[{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10615,"experimentAnswers.text":"150 μg/incubation","experimentAnswers.answerId":null,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":2,"experimentAnswers.question.id":2,"experimentAnswers.question.text":"Protein concentration","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10609,"experimentAnswers.text":null,"experimentAnswers.answerId":1,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":3,"experimentAnswers.question.id":3,"experimentAnswers.question.text":"Test system preparation","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":1,"experimentAnswers.question.answers.text":"Commercially available","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":3,"experimentAnswers.answer.id":1,"experimentAnswers.answer.text":"Commercially available","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":3},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10609,"experimentAnswers.text":null,"experimentAnswers.answerId":1,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":3,"experimentAnswers.question.id":3,"experimentAnswers.question.text":"Test system preparation","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":2,"experimentAnswers.question.answers.text":"In-house preparation","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":3,"experimentAnswers.answer.id":1,"experimentAnswers.answer.text":"Commercially available","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":3},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10617,"experimentAnswers.text":"250  μL","experimentAnswers.answerId":null,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":5,"experimentAnswers.question.id":5,"experimentAnswers.question.text":"Incubation volume","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10618,"experimentAnswers.text":"120 min","experimentAnswers.answerId":null,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":6,"experimentAnswers.question.id":6,"experimentAnswers.question.text":"Incubation time","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10610,"experimentAnswers.text":null,"experimentAnswers.answerId":3,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":7,"experimentAnswers.question.id":7,"experimentAnswers.question.text":"Co-factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":3,"experimentAnswers.question.answers.text":"MgCl2","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":7,"experimentAnswers.answer.id":3,"experimentAnswers.answer.text":"MgCl2","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10610,"experimentAnswers.text":null,"experimentAnswers.answerId":3,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":7,"experimentAnswers.question.id":7,"experimentAnswers.question.text":"Co-factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":4,"experimentAnswers.question.answers.text":"NAD","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":7,"experimentAnswers.answer.id":3,"experimentAnswers.answer.text":"MgCl2","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10610,"experimentAnswers.text":null,"experimentAnswers.answerId":3,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":7,"experimentAnswers.question.id":7,"experimentAnswers.question.text":"Co-factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":5,"experimentAnswers.question.answers.text":"NADH","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":7,"experimentAnswers.answer.id":3,"experimentAnswers.answer.text":"MgCl2","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10610,"experimentAnswers.text":null,"experimentAnswers.answerId":3,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":7,"experimentAnswers.question.id":7,"experimentAnswers.question.text":"Co-factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":6,"experimentAnswers.question.answers.text":"NADPH","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":7,"experimentAnswers.answer.id":3,"experimentAnswers.answer.text":"MgCl2","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10610,"experimentAnswers.text":null,"experimentAnswers.answerId":3,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":7,"experimentAnswers.question.id":7,"experimentAnswers.question.text":"Co-factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":7,"experimentAnswers.question.answers.text":"NADPH regenerating system","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":7,"experimentAnswers.answer.id":3,"experimentAnswers.answer.text":"MgCl2","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10610,"experimentAnswers.text":null,"experimentAnswers.answerId":3,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":7,"experimentAnswers.question.id":7,"experimentAnswers.question.text":"Co-factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":8,"experimentAnswers.question.answers.text":"P450 reductase","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":7,"experimentAnswers.answer.id":3,"experimentAnswers.answer.text":"MgCl2","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10611,"experimentAnswers.text":null,"experimentAnswers.answerId":9,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":8,"experimentAnswers.question.id":8,"experimentAnswers.question.text":"Co-substrate","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":11,"experimentAnswers.question.answers.text":"GSH","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":8,"experimentAnswers.answer.id":9,"experimentAnswers.answer.text":"UDPGA","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":8},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10611,"experimentAnswers.text":null,"experimentAnswers.answerId":9,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":8,"experimentAnswers.question.id":8,"experimentAnswers.question.text":"Co-substrate","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":10,"experimentAnswers.question.answers.text":"PAPS","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":8,"experimentAnswers.answer.id":9,"experimentAnswers.answer.text":"UDPGA","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":8},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10611,"experimentAnswers.text":null,"experimentAnswers.answerId":9,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":8,"experimentAnswers.question.id":8,"experimentAnswers.question.text":"Co-substrate","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":9,"experimentAnswers.question.answers.text":"UDPGA","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":8,"experimentAnswers.answer.id":9,"experimentAnswers.answer.text":"UDPGA","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":8},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10612,"experimentAnswers.text":null,"experimentAnswers.answerId":13,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":9,"experimentAnswers.question.id":9,"experimentAnswers.question.text":"Protein linearity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":12,"experimentAnswers.question.answers.text":"Available","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":9,"experimentAnswers.answer.id":13,"experimentAnswers.answer.text":"Not available","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":9},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10612,"experimentAnswers.text":null,"experimentAnswers.answerId":13,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":9,"experimentAnswers.question.id":9,"experimentAnswers.question.text":"Protein linearity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":13,"experimentAnswers.question.answers.text":"Not available","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":9,"experimentAnswers.answer.id":13,"experimentAnswers.answer.text":"Not available","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":9},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10613,"experimentAnswers.text":null,"experimentAnswers.answerId":15,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":10,"experimentAnswers.question.id":10,"experimentAnswers.question.text":"Time linearity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":14,"experimentAnswers.question.answers.text":"Available","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":10,"experimentAnswers.answer.id":15,"experimentAnswers.answer.text":"Not available","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":10},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10613,"experimentAnswers.text":null,"experimentAnswers.answerId":15,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":10,"experimentAnswers.question.id":10,"experimentAnswers.question.text":"Time linearity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":15,"experimentAnswers.question.answers.text":"Not available","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":10,"experimentAnswers.answer.id":15,"experimentAnswers.answer.text":"Not available","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":10},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10614,"experimentAnswers.text":"350  μM","experimentAnswers.answerId":null,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":11,"experimentAnswers.question.id":11,"experimentAnswers.question.text":"Object concentrations tested","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":590,"uid":"NPDI-bX8XPA","name":"No inhibition of UGT2B7 by ketamine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>IC50 &gt; 10 &mu;M are low potential inhibitors. <br />1 &mu;M &lt; IC50 &lt; 10 &mu;M are moderate potential inhibitors.&nbsp;<br /> IC50 &lt; 1 &mu;M are high potential inhibitors.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"The amount of protein, the incubation time and the concentration of 4-MU used in the measurement of 4-MU glucuronidation were described in the method by Uchaipichat et al.<br /><br />Microsomes expressing recombinant human UGT1A1 and UGT2B7 were obtained from BD Biosciences (Woburn, MA, United States);incubations (total volume 250 μL) contained phosphate buffer (100 mM) (pH 7.4), MgCl <sub>2</sub> (5 mM), cell lysate (83.3 μg/mL for UGT1A1 or 62.5 μg/mL for UGT2B7), UDPGA (5 mM), and 4-MU (substrate) (100 μM for UGT1A1 assay or 350 μM for UGT2B7 assay).<br /><br />Control=no inhibitor","resultsComment":"Concentration of precipitant and % inhibition of UGT2B7 (values estimated from figure 5)<br />0.01 μM: -5 ± 6%<br />0.1 μM: 4 ± 5% <br />1 μM: 11 ± 5% <br />10 μM: 34 ± 3% (p &lt; 0.05)<br />100 μM: 70 ± 1% (p &lt; 0.05)<br />1000 μM: See above data","internalComment":"Experimental conditions tab: Uchaipichat et al  can be found here http://dmd.aspetjournals.org/content/dmd/32/4/413.full.pdf","objectCompoundId":70,"objectMetaboliteCompoundId":73,"precipitantCompoundId":191,"cytochromeB5Id":4,"studyId":124,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":1,"experimentType.name":"In Vitro Enzyme Inhibition","experimentType.isInVitro":true,"experimentType.isTransporter":false,"experimentType.isEnzyme":true,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000058","objectCompound.id":70,"objectCompound.name":"4-methylumbelliferone","objectCompound.unii":null,"objectCompound.inChIKey":"HSHNITRMYYLLCV-UHFFFAOYSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":191,"precipitantCompound.name":"ketamine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"YQEZLKZALYSWHR-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":73,"objectMetaboliteCompound.name":"4-methylumbelliferone glucuronide","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"ARQXEQLMMNGFDU-JHZZJYKESA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":22,"enzymes.name":"UGT2B7","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":22,"enzymes.experiment_enzyme_xref.experimentId":590,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":124,"study.uid":"NPDI-9C7QHg","study.name":"Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms","study.napdiIdentifier":null,"study.overallSummary":"<p>Background:  Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. </p>\r\n<p>Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.</p>\r\n<p>Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. </p>\r\n<p>Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.</p>\r\n<p>Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.</p>","study.pubmedId":26692748,"study.embaseId":2015485354,"study.croIdentifier":"Centre for Drug Research","study.croInformation":"Universiti Sains Malaysia","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"Positive data entered","study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","study.naturalProduct.binomial":"Mitragyna speciosa","study.naturalProduct.name":"Kratom","study.naturalProduct.itis":null,"study.naturalProduct.srs":"d469b67d-e9a6-459f-b209-c59451936336","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":14,"testSystem.name":"Baculovirus-insect cells","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":3,"testSystem.category.id":3,"testSystem.category.name":"Recombinant expression system","testSystem.category.sortOrder":3,"testSystem.category.requiresCytochromeB5":true,"cytochromeB5.id":4,"cytochromeB5.name":"Not available","cytochromeB5.sortOrder":4,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":10616,"experimentAnswers.text":"0.01-1000 μM","experimentAnswers.answerId":null,"experimentAnswers.experimentId":590,"experimentAnswers.questionId":15,"experimentAnswers.question.id":15,"experimentAnswers.question.text":"Precipitant concentrations tested","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null}]