[{"id":595,"uid":"NPDI-ypADxQ","name":"No inhibition of CYP3A4 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>High probability of interaction if their IC50 values are less than 1 &micro;M. If IC50 values are between 1 and 10 &micro;M, they have moderate possibility in interaction. Low drug-drug interactions if their IC50 values are greater than 10 &micro;M.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"Mitragynine was isolated in-house. This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.","resultsComment":"IC50 values from Table 1, Ki values from Table 3<br /><br />% enzyme inhibition versus precipitant concentration:<br />Values estimated from Figure 2. In some cases, SEM could not be estimated from the provided figure.<br /><br />0.02 μM: -24 ± 0%<br />0.2 μM: -21 ± 5%<br />2 μM: -2 ± 1%<br />20 μM: 25 ± 2%<br />200 μM: See above data","internalComment":null,"objectCompoundId":196,"objectMetaboliteCompoundId":194,"precipitantCompoundId":94,"cytochromeB5Id":1,"studyId":128,"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":196,"objectCompound.name":"luciferin 6’benzyl ether (luciferin-be)","objectCompound.unii":null,"objectCompound.inChIKey":null,"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":94,"precipitantCompound.name":"mitragynine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"LELBFTMXCIIKKX-QVRQZEMUSA-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":194,"objectMetaboliteCompound.name":"luciferin","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":"AKA d-luciferin","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":13,"enzymes.name":"CYP3A4","enzymes.conceptId":4306811,"enzymes.experiment_enzyme_xref.enzymeId":13,"enzymes.experiment_enzyme_xref.experimentId":595,"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":128,"study.uid":"NPDI-XtvOZQ","study.name":"Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities","study.napdiIdentifier":null,"study.overallSummary":"Context: To date, many findings reveal that most of the modern drugs have the ability to interact with herbal drugs. <br /><br />Aims: This study was conducted to determine the inhibitory effects of mitragynine on cytochrome P450 2C9, 2D6 and 3A4 activities. <br /><br />Methods and Material: The in vitro study was conducted using a high-throughput luminescence assay. <br /><br />Statistical Analysis: Statistical analysis was conducted using one-way ANOVA and Dunnett's test with P &lt; 0.05 vs. control. The IC values were calculated using the GraphPad Prism 5 (Version 5.01, GraphPad Software, Inc., USA)<br /><br />Results: Assessment using recombinant enzymes showed that mitragynine gave the strongest inhibitory effect on CYP2D6 with an IC50 value of 0.45±0.33 mM, followed by CYP2C9 and CYP3A4 with IC50 values of 9.70±4.80 and 41.32±6.74 µM respectively. Positive inhibitors appropriate for CYP2C9, CYP2D6, and CYP3A4 which are sulfaphenazole, quinidine and ketoconazole were used respectively. Vmax values of CYP2C9, CYP2D6 and CYP3A4 were 0.0005, 0.01155 and 0.0137 µM luciferin formed/pmol/min respectively. Km values of CYP2C9, CYP2D6, and CYP3A4 were 32.65, 56.01, and 103.30 µM respectively. Mitragynine noncompetitively inhibits CYP2C9 and CYP2D6 activities with the Ki values of 61.48 and 12.86 µM respectively. On the other hand, mitragynine inhibits CYP3A4 competitively with a Ki value of 379.18 µM.<br /><br />Conclusions: The findings of this study reveal that mitragynine might inhibit cytochrome P450 enzyme activities, specifically CYP2D6. Therefore, administration of mitragynine together with herbal or modern drugs which follow the same metabolic pathway may contribute to herb-drug interactions.","study.pubmedId":24174816,"study.embaseId":2013651136,"study.croIdentifier":"Centre for Drug Research, Penang","study.croInformation":"Universiti Sains Malaysia","study.dateStart":"2010-09-01T00:00:00.000Z","study.dateEnd":"2011-07-31T00:00:00.000Z","study.internalComment":null,"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":1,"cytochromeB5.name":"Co-expressed","cytochromeB5.sortOrder":1,"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":10799,"experimentAnswers.text":null,"experimentAnswers.answerId":1,"experimentAnswers.experimentId":595,"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":595,"uid":"NPDI-ypADxQ","name":"No inhibition of CYP3A4 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>High probability of interaction if their IC50 values are less than 1 &micro;M. If IC50 values are between 1 and 10 &micro;M, they have moderate possibility in interaction. Low drug-drug interactions if their IC50 values are greater than 10 &micro;M.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"Mitragynine was isolated in-house. This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.","resultsComment":"IC50 values from Table 1, Ki values from Table 3<br /><br />% enzyme inhibition versus precipitant concentration:<br />Values estimated from Figure 2. In some cases, SEM could not be estimated from the provided figure.<br /><br />0.02 μM: -24 ± 0%<br />0.2 μM: -21 ± 5%<br />2 μM: -2 ± 1%<br />20 μM: 25 ± 2%<br />200 μM: See above data","internalComment":null,"objectCompoundId":196,"objectMetaboliteCompoundId":194,"precipitantCompoundId":94,"cytochromeB5Id":1,"studyId":128,"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":196,"objectCompound.name":"luciferin 6’benzyl ether (luciferin-be)","objectCompound.unii":null,"objectCompound.inChIKey":null,"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":94,"precipitantCompound.name":"mitragynine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"LELBFTMXCIIKKX-QVRQZEMUSA-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":194,"objectMetaboliteCompound.name":"luciferin","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":"AKA d-luciferin","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":13,"enzymes.name":"CYP3A4","enzymes.conceptId":4306811,"enzymes.experiment_enzyme_xref.enzymeId":13,"enzymes.experiment_enzyme_xref.experimentId":595,"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":128,"study.uid":"NPDI-XtvOZQ","study.name":"Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities","study.napdiIdentifier":null,"study.overallSummary":"Context: To date, many findings reveal that most of the modern drugs have the ability to interact with herbal drugs. <br /><br />Aims: This study was conducted to determine the inhibitory effects of mitragynine on cytochrome P450 2C9, 2D6 and 3A4 activities. <br /><br />Methods and Material: The in vitro study was conducted using a high-throughput luminescence assay. <br /><br />Statistical Analysis: Statistical analysis was conducted using one-way ANOVA and Dunnett's test with P &lt; 0.05 vs. control. The IC values were calculated using the GraphPad Prism 5 (Version 5.01, GraphPad Software, Inc., USA)<br /><br />Results: Assessment using recombinant enzymes showed that mitragynine gave the strongest inhibitory effect on CYP2D6 with an IC50 value of 0.45±0.33 mM, followed by CYP2C9 and CYP3A4 with IC50 values of 9.70±4.80 and 41.32±6.74 µM respectively. Positive inhibitors appropriate for CYP2C9, CYP2D6, and CYP3A4 which are sulfaphenazole, quinidine and ketoconazole were used respectively. Vmax values of CYP2C9, CYP2D6 and CYP3A4 were 0.0005, 0.01155 and 0.0137 µM luciferin formed/pmol/min respectively. Km values of CYP2C9, CYP2D6, and CYP3A4 were 32.65, 56.01, and 103.30 µM respectively. Mitragynine noncompetitively inhibits CYP2C9 and CYP2D6 activities with the Ki values of 61.48 and 12.86 µM respectively. On the other hand, mitragynine inhibits CYP3A4 competitively with a Ki value of 379.18 µM.<br /><br />Conclusions: The findings of this study reveal that mitragynine might inhibit cytochrome P450 enzyme activities, specifically CYP2D6. Therefore, administration of mitragynine together with herbal or modern drugs which follow the same metabolic pathway may contribute to herb-drug interactions.","study.pubmedId":24174816,"study.embaseId":2013651136,"study.croIdentifier":"Centre for Drug Research, Penang","study.croInformation":"Universiti Sains Malaysia","study.dateStart":"2010-09-01T00:00:00.000Z","study.dateEnd":"2011-07-31T00:00:00.000Z","study.internalComment":null,"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":1,"cytochromeB5.name":"Co-expressed","cytochromeB5.sortOrder":1,"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":10799,"experimentAnswers.text":null,"experimentAnswers.answerId":1,"experimentAnswers.experimentId":595,"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":595,"uid":"NPDI-ypADxQ","name":"No inhibition of CYP3A4 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>High probability of interaction if their IC50 values are less than 1 &micro;M. If IC50 values are between 1 and 10 &micro;M, they have moderate possibility in interaction. Low drug-drug interactions if their IC50 values are greater than 10 &micro;M.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"Mitragynine was isolated in-house. This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.","resultsComment":"IC50 values from Table 1, Ki values from Table 3<br /><br />% enzyme inhibition versus precipitant concentration:<br />Values estimated from Figure 2. In some cases, SEM could not be estimated from the provided figure.<br /><br />0.02 μM: -24 ± 0%<br />0.2 μM: -21 ± 5%<br />2 μM: -2 ± 1%<br />20 μM: 25 ± 2%<br />200 μM: See above data","internalComment":null,"objectCompoundId":196,"objectMetaboliteCompoundId":194,"precipitantCompoundId":94,"cytochromeB5Id":1,"studyId":128,"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":196,"objectCompound.name":"luciferin 6’benzyl ether (luciferin-be)","objectCompound.unii":null,"objectCompound.inChIKey":null,"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":94,"precipitantCompound.name":"mitragynine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"LELBFTMXCIIKKX-QVRQZEMUSA-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":194,"objectMetaboliteCompound.name":"luciferin","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":"AKA d-luciferin","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":13,"enzymes.name":"CYP3A4","enzymes.conceptId":4306811,"enzymes.experiment_enzyme_xref.enzymeId":13,"enzymes.experiment_enzyme_xref.experimentId":595,"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":128,"study.uid":"NPDI-XtvOZQ","study.name":"Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities","study.napdiIdentifier":null,"study.overallSummary":"Context: To date, many findings reveal that most of the modern drugs have the ability to interact with herbal drugs. <br /><br />Aims: This study was conducted to determine the inhibitory effects of mitragynine on cytochrome P450 2C9, 2D6 and 3A4 activities. <br /><br />Methods and Material: The in vitro study was conducted using a high-throughput luminescence assay. <br /><br />Statistical Analysis: Statistical analysis was conducted using one-way ANOVA and Dunnett's test with P &lt; 0.05 vs. control. The IC values were calculated using the GraphPad Prism 5 (Version 5.01, GraphPad Software, Inc., USA)<br /><br />Results: Assessment using recombinant enzymes showed that mitragynine gave the strongest inhibitory effect on CYP2D6 with an IC50 value of 0.45±0.33 mM, followed by CYP2C9 and CYP3A4 with IC50 values of 9.70±4.80 and 41.32±6.74 µM respectively. Positive inhibitors appropriate for CYP2C9, CYP2D6, and CYP3A4 which are sulfaphenazole, quinidine and ketoconazole were used respectively. Vmax values of CYP2C9, CYP2D6 and CYP3A4 were 0.0005, 0.01155 and 0.0137 µM luciferin formed/pmol/min respectively. Km values of CYP2C9, CYP2D6, and CYP3A4 were 32.65, 56.01, and 103.30 µM respectively. Mitragynine noncompetitively inhibits CYP2C9 and CYP2D6 activities with the Ki values of 61.48 and 12.86 µM respectively. On the other hand, mitragynine inhibits CYP3A4 competitively with a Ki value of 379.18 µM.<br /><br />Conclusions: The findings of this study reveal that mitragynine might inhibit cytochrome P450 enzyme activities, specifically CYP2D6. Therefore, administration of mitragynine together with herbal or modern drugs which follow the same metabolic pathway may contribute to herb-drug interactions.","study.pubmedId":24174816,"study.embaseId":2013651136,"study.croIdentifier":"Centre for Drug Research, Penang","study.croInformation":"Universiti Sains Malaysia","study.dateStart":"2010-09-01T00:00:00.000Z","study.dateEnd":"2011-07-31T00:00:00.000Z","study.internalComment":null,"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":1,"cytochromeB5.name":"Co-expressed","cytochromeB5.sortOrder":1,"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":10804,"experimentAnswers.text":"50 min","experimentAnswers.answerId":null,"experimentAnswers.experimentId":595,"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":595,"uid":"NPDI-ypADxQ","name":"No inhibition of CYP3A4 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>High probability of interaction if their IC50 values are less than 1 &micro;M. If IC50 values are between 1 and 10 &micro;M, they have moderate possibility in interaction. Low drug-drug interactions if their IC50 values are greater than 10 &micro;M.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"Mitragynine was isolated in-house. This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.","resultsComment":"IC50 values from Table 1, Ki values from Table 3<br /><br />% enzyme inhibition versus precipitant concentration:<br />Values estimated from Figure 2. In some cases, SEM could not be estimated from the provided figure.<br /><br />0.02 μM: -24 ± 0%<br />0.2 μM: -21 ± 5%<br />2 μM: -2 ± 1%<br />20 μM: 25 ± 2%<br />200 μM: See above data","internalComment":null,"objectCompoundId":196,"objectMetaboliteCompoundId":194,"precipitantCompoundId":94,"cytochromeB5Id":1,"studyId":128,"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":196,"objectCompound.name":"luciferin 6’benzyl ether (luciferin-be)","objectCompound.unii":null,"objectCompound.inChIKey":null,"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":94,"precipitantCompound.name":"mitragynine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"LELBFTMXCIIKKX-QVRQZEMUSA-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":194,"objectMetaboliteCompound.name":"luciferin","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":"AKA d-luciferin","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":13,"enzymes.name":"CYP3A4","enzymes.conceptId":4306811,"enzymes.experiment_enzyme_xref.enzymeId":13,"enzymes.experiment_enzyme_xref.experimentId":595,"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":128,"study.uid":"NPDI-XtvOZQ","study.name":"Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities","study.napdiIdentifier":null,"study.overallSummary":"Context: To date, many findings reveal that most of the modern drugs have the ability to interact with herbal drugs. <br /><br />Aims: This study was conducted to determine the inhibitory effects of mitragynine on cytochrome P450 2C9, 2D6 and 3A4 activities. <br /><br />Methods and Material: The in vitro study was conducted using a high-throughput luminescence assay. <br /><br />Statistical Analysis: Statistical analysis was conducted using one-way ANOVA and Dunnett's test with P &lt; 0.05 vs. control. The IC values were calculated using the GraphPad Prism 5 (Version 5.01, GraphPad Software, Inc., USA)<br /><br />Results: Assessment using recombinant enzymes showed that mitragynine gave the strongest inhibitory effect on CYP2D6 with an IC50 value of 0.45±0.33 mM, followed by CYP2C9 and CYP3A4 with IC50 values of 9.70±4.80 and 41.32±6.74 µM respectively. Positive inhibitors appropriate for CYP2C9, CYP2D6, and CYP3A4 which are sulfaphenazole, quinidine and ketoconazole were used respectively. Vmax values of CYP2C9, CYP2D6 and CYP3A4 were 0.0005, 0.01155 and 0.0137 µM luciferin formed/pmol/min respectively. Km values of CYP2C9, CYP2D6, and CYP3A4 were 32.65, 56.01, and 103.30 µM respectively. Mitragynine noncompetitively inhibits CYP2C9 and CYP2D6 activities with the Ki values of 61.48 and 12.86 µM respectively. On the other hand, mitragynine inhibits CYP3A4 competitively with a Ki value of 379.18 µM.<br /><br />Conclusions: The findings of this study reveal that mitragynine might inhibit cytochrome P450 enzyme activities, specifically CYP2D6. Therefore, administration of mitragynine together with herbal or modern drugs which follow the same metabolic pathway may contribute to herb-drug interactions.","study.pubmedId":24174816,"study.embaseId":2013651136,"study.croIdentifier":"Centre for Drug Research, Penang","study.croInformation":"Universiti Sains Malaysia","study.dateStart":"2010-09-01T00:00:00.000Z","study.dateEnd":"2011-07-31T00:00:00.000Z","study.internalComment":null,"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":1,"cytochromeB5.name":"Co-expressed","cytochromeB5.sortOrder":1,"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":10800,"experimentAnswers.text":null,"experimentAnswers.answerId":7,"experimentAnswers.experimentId":595,"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":7,"experimentAnswers.answer.text":"NADPH regenerating system","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":595,"uid":"NPDI-ypADxQ","name":"No inhibition of CYP3A4 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>High probability of interaction if their IC50 values are less than 1 &micro;M. If IC50 values are between 1 and 10 &micro;M, they have moderate possibility in interaction. Low drug-drug interactions if their IC50 values are greater than 10 &micro;M.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"Mitragynine was isolated in-house. This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.","resultsComment":"IC50 values from Table 1, Ki values from Table 3<br /><br />% enzyme inhibition versus precipitant concentration:<br />Values estimated from Figure 2. In some cases, SEM could not be estimated from the provided figure.<br /><br />0.02 μM: -24 ± 0%<br />0.2 μM: -21 ± 5%<br />2 μM: -2 ± 1%<br />20 μM: 25 ± 2%<br />200 μM: See above data","internalComment":null,"objectCompoundId":196,"objectMetaboliteCompoundId":194,"precipitantCompoundId":94,"cytochromeB5Id":1,"studyId":128,"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":196,"objectCompound.name":"luciferin 6’benzyl ether (luciferin-be)","objectCompound.unii":null,"objectCompound.inChIKey":null,"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":94,"precipitantCompound.name":"mitragynine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"LELBFTMXCIIKKX-QVRQZEMUSA-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":194,"objectMetaboliteCompound.name":"luciferin","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":"AKA d-luciferin","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":13,"enzymes.name":"CYP3A4","enzymes.conceptId":4306811,"enzymes.experiment_enzyme_xref.enzymeId":13,"enzymes.experiment_enzyme_xref.experimentId":595,"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":128,"study.uid":"NPDI-XtvOZQ","study.name":"Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities","study.napdiIdentifier":null,"study.overallSummary":"Context: To date, many findings reveal that most of the modern drugs have the ability to interact with herbal drugs. <br /><br />Aims: This study was conducted to determine the inhibitory effects of mitragynine on cytochrome P450 2C9, 2D6 and 3A4 activities. <br /><br />Methods and Material: The in vitro study was conducted using a high-throughput luminescence assay. <br /><br />Statistical Analysis: Statistical analysis was conducted using one-way ANOVA and Dunnett's test with P &lt; 0.05 vs. control. The IC values were calculated using the GraphPad Prism 5 (Version 5.01, GraphPad Software, Inc., USA)<br /><br />Results: Assessment using recombinant enzymes showed that mitragynine gave the strongest inhibitory effect on CYP2D6 with an IC50 value of 0.45±0.33 mM, followed by CYP2C9 and CYP3A4 with IC50 values of 9.70±4.80 and 41.32±6.74 µM respectively. Positive inhibitors appropriate for CYP2C9, CYP2D6, and CYP3A4 which are sulfaphenazole, quinidine and ketoconazole were used respectively. Vmax values of CYP2C9, CYP2D6 and CYP3A4 were 0.0005, 0.01155 and 0.0137 µM luciferin formed/pmol/min respectively. Km values of CYP2C9, CYP2D6, and CYP3A4 were 32.65, 56.01, and 103.30 µM respectively. Mitragynine noncompetitively inhibits CYP2C9 and CYP2D6 activities with the Ki values of 61.48 and 12.86 µM respectively. On the other hand, mitragynine inhibits CYP3A4 competitively with a Ki value of 379.18 µM.<br /><br />Conclusions: The findings of this study reveal that mitragynine might inhibit cytochrome P450 enzyme activities, specifically CYP2D6. Therefore, administration of mitragynine together with herbal or modern drugs which follow the same metabolic pathway may contribute to herb-drug interactions.","study.pubmedId":24174816,"study.embaseId":2013651136,"study.croIdentifier":"Centre for Drug Research, Penang","study.croInformation":"Universiti Sains Malaysia","study.dateStart":"2010-09-01T00:00:00.000Z","study.dateEnd":"2011-07-31T00:00:00.000Z","study.internalComment":null,"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":1,"cytochromeB5.name":"Co-expressed","cytochromeB5.sortOrder":1,"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":10800,"experimentAnswers.text":null,"experimentAnswers.answerId":7,"experimentAnswers.experimentId":595,"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":7,"experimentAnswers.answer.text":"NADPH regenerating system","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":595,"uid":"NPDI-ypADxQ","name":"No inhibition of CYP3A4 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>High probability of interaction if their IC50 values are less than 1 &micro;M. If IC50 values are between 1 and 10 &micro;M, they have moderate possibility in interaction. Low drug-drug interactions if their IC50 values are greater than 10 &micro;M.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"Mitragynine was isolated in-house. This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.","resultsComment":"IC50 values from Table 1, Ki values from Table 3<br /><br />% enzyme inhibition versus precipitant concentration:<br />Values estimated from Figure 2. In some cases, SEM could not be estimated from the provided figure.<br /><br />0.02 μM: -24 ± 0%<br />0.2 μM: -21 ± 5%<br />2 μM: -2 ± 1%<br />20 μM: 25 ± 2%<br />200 μM: See above data","internalComment":null,"objectCompoundId":196,"objectMetaboliteCompoundId":194,"precipitantCompoundId":94,"cytochromeB5Id":1,"studyId":128,"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":196,"objectCompound.name":"luciferin 6’benzyl ether (luciferin-be)","objectCompound.unii":null,"objectCompound.inChIKey":null,"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":94,"precipitantCompound.name":"mitragynine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"LELBFTMXCIIKKX-QVRQZEMUSA-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":194,"objectMetaboliteCompound.name":"luciferin","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":"AKA d-luciferin","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":13,"enzymes.name":"CYP3A4","enzymes.conceptId":4306811,"enzymes.experiment_enzyme_xref.enzymeId":13,"enzymes.experiment_enzyme_xref.experimentId":595,"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":128,"study.uid":"NPDI-XtvOZQ","study.name":"Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities","study.napdiIdentifier":null,"study.overallSummary":"Context: To date, many findings reveal that most of the modern drugs have the ability to interact with herbal drugs. <br /><br />Aims: This study was conducted to determine the inhibitory effects of mitragynine on cytochrome P450 2C9, 2D6 and 3A4 activities. <br /><br />Methods and Material: The in vitro study was conducted using a high-throughput luminescence assay. <br /><br />Statistical Analysis: Statistical analysis was conducted using one-way ANOVA and Dunnett's test with P &lt; 0.05 vs. control. The IC values were calculated using the GraphPad Prism 5 (Version 5.01, GraphPad Software, Inc., USA)<br /><br />Results: Assessment using recombinant enzymes showed that mitragynine gave the strongest inhibitory effect on CYP2D6 with an IC50 value of 0.45±0.33 mM, followed by CYP2C9 and CYP3A4 with IC50 values of 9.70±4.80 and 41.32±6.74 µM respectively. Positive inhibitors appropriate for CYP2C9, CYP2D6, and CYP3A4 which are sulfaphenazole, quinidine and ketoconazole were used respectively. Vmax values of CYP2C9, CYP2D6 and CYP3A4 were 0.0005, 0.01155 and 0.0137 µM luciferin formed/pmol/min respectively. Km values of CYP2C9, CYP2D6, and CYP3A4 were 32.65, 56.01, and 103.30 µM respectively. Mitragynine noncompetitively inhibits CYP2C9 and CYP2D6 activities with the Ki values of 61.48 and 12.86 µM respectively. On the other hand, mitragynine inhibits CYP3A4 competitively with a Ki value of 379.18 µM.<br /><br />Conclusions: The findings of this study reveal that mitragynine might inhibit cytochrome P450 enzyme activities, specifically CYP2D6. Therefore, administration of mitragynine together with herbal or modern drugs which follow the same metabolic pathway may contribute to herb-drug interactions.","study.pubmedId":24174816,"study.embaseId":2013651136,"study.croIdentifier":"Centre for Drug Research, Penang","study.croInformation":"Universiti Sains Malaysia","study.dateStart":"2010-09-01T00:00:00.000Z","study.dateEnd":"2011-07-31T00:00:00.000Z","study.internalComment":null,"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":1,"cytochromeB5.name":"Co-expressed","cytochromeB5.sortOrder":1,"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":10800,"experimentAnswers.text":null,"experimentAnswers.answerId":7,"experimentAnswers.experimentId":595,"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":7,"experimentAnswers.answer.text":"NADPH regenerating system","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":595,"uid":"NPDI-ypADxQ","name":"No inhibition of CYP3A4 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>High probability of interaction if their IC50 values are less than 1 &micro;M. If IC50 values are between 1 and 10 &micro;M, they have moderate possibility in interaction. Low drug-drug interactions if their IC50 values are greater than 10 &micro;M.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"Mitragynine was isolated in-house. This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.","resultsComment":"IC50 values from Table 1, Ki values from Table 3<br /><br />% enzyme inhibition versus precipitant concentration:<br />Values estimated from Figure 2. In some cases, SEM could not be estimated from the provided figure.<br /><br />0.02 μM: -24 ± 0%<br />0.2 μM: -21 ± 5%<br />2 μM: -2 ± 1%<br />20 μM: 25 ± 2%<br />200 μM: See above data","internalComment":null,"objectCompoundId":196,"objectMetaboliteCompoundId":194,"precipitantCompoundId":94,"cytochromeB5Id":1,"studyId":128,"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":196,"objectCompound.name":"luciferin 6’benzyl ether (luciferin-be)","objectCompound.unii":null,"objectCompound.inChIKey":null,"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":94,"precipitantCompound.name":"mitragynine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"LELBFTMXCIIKKX-QVRQZEMUSA-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":194,"objectMetaboliteCompound.name":"luciferin","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":"AKA d-luciferin","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":13,"enzymes.name":"CYP3A4","enzymes.conceptId":4306811,"enzymes.experiment_enzyme_xref.enzymeId":13,"enzymes.experiment_enzyme_xref.experimentId":595,"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":128,"study.uid":"NPDI-XtvOZQ","study.name":"Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities","study.napdiIdentifier":null,"study.overallSummary":"Context: To date, many findings reveal that most of the modern drugs have the ability to interact with herbal drugs. <br /><br />Aims: This study was conducted to determine the inhibitory effects of mitragynine on cytochrome P450 2C9, 2D6 and 3A4 activities. <br /><br />Methods and Material: The in vitro study was conducted using a high-throughput luminescence assay. <br /><br />Statistical Analysis: Statistical analysis was conducted using one-way ANOVA and Dunnett's test with P &lt; 0.05 vs. control. The IC values were calculated using the GraphPad Prism 5 (Version 5.01, GraphPad Software, Inc., USA)<br /><br />Results: Assessment using recombinant enzymes showed that mitragynine gave the strongest inhibitory effect on CYP2D6 with an IC50 value of 0.45±0.33 mM, followed by CYP2C9 and CYP3A4 with IC50 values of 9.70±4.80 and 41.32±6.74 µM respectively. Positive inhibitors appropriate for CYP2C9, CYP2D6, and CYP3A4 which are sulfaphenazole, quinidine and ketoconazole were used respectively. Vmax values of CYP2C9, CYP2D6 and CYP3A4 were 0.0005, 0.01155 and 0.0137 µM luciferin formed/pmol/min respectively. Km values of CYP2C9, CYP2D6, and CYP3A4 were 32.65, 56.01, and 103.30 µM respectively. Mitragynine noncompetitively inhibits CYP2C9 and CYP2D6 activities with the Ki values of 61.48 and 12.86 µM respectively. On the other hand, mitragynine inhibits CYP3A4 competitively with a Ki value of 379.18 µM.<br /><br />Conclusions: The findings of this study reveal that mitragynine might inhibit cytochrome P450 enzyme activities, specifically CYP2D6. Therefore, administration of mitragynine together with herbal or modern drugs which follow the same metabolic pathway may contribute to herb-drug interactions.","study.pubmedId":24174816,"study.embaseId":2013651136,"study.croIdentifier":"Centre for Drug Research, Penang","study.croInformation":"Universiti Sains Malaysia","study.dateStart":"2010-09-01T00:00:00.000Z","study.dateEnd":"2011-07-31T00:00:00.000Z","study.internalComment":null,"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":1,"cytochromeB5.name":"Co-expressed","cytochromeB5.sortOrder":1,"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":10800,"experimentAnswers.text":null,"experimentAnswers.answerId":7,"experimentAnswers.experimentId":595,"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":7,"experimentAnswers.answer.text":"NADPH regenerating system","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":595,"uid":"NPDI-ypADxQ","name":"No inhibition of CYP3A4 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>High probability of interaction if their IC50 values are less than 1 &micro;M. If IC50 values are between 1 and 10 &micro;M, they have moderate possibility in interaction. Low drug-drug interactions if their IC50 values are greater than 10 &micro;M.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"Mitragynine was isolated in-house. This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.","resultsComment":"IC50 values from Table 1, Ki values from Table 3<br /><br />% enzyme inhibition versus precipitant concentration:<br />Values estimated from Figure 2. In some cases, SEM could not be estimated from the provided figure.<br /><br />0.02 μM: -24 ± 0%<br />0.2 μM: -21 ± 5%<br />2 μM: -2 ± 1%<br />20 μM: 25 ± 2%<br />200 μM: See above data","internalComment":null,"objectCompoundId":196,"objectMetaboliteCompoundId":194,"precipitantCompoundId":94,"cytochromeB5Id":1,"studyId":128,"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":196,"objectCompound.name":"luciferin 6’benzyl ether (luciferin-be)","objectCompound.unii":null,"objectCompound.inChIKey":null,"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":94,"precipitantCompound.name":"mitragynine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"LELBFTMXCIIKKX-QVRQZEMUSA-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":194,"objectMetaboliteCompound.name":"luciferin","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":"AKA d-luciferin","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":13,"enzymes.name":"CYP3A4","enzymes.conceptId":4306811,"enzymes.experiment_enzyme_xref.enzymeId":13,"enzymes.experiment_enzyme_xref.experimentId":595,"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":128,"study.uid":"NPDI-XtvOZQ","study.name":"Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities","study.napdiIdentifier":null,"study.overallSummary":"Context: To date, many findings reveal that most of the modern drugs have the ability to interact with herbal drugs. <br /><br />Aims: This study was conducted to determine the inhibitory effects of mitragynine on cytochrome P450 2C9, 2D6 and 3A4 activities. <br /><br />Methods and Material: The in vitro study was conducted using a high-throughput luminescence assay. <br /><br />Statistical Analysis: Statistical analysis was conducted using one-way ANOVA and Dunnett's test with P &lt; 0.05 vs. control. The IC values were calculated using the GraphPad Prism 5 (Version 5.01, GraphPad Software, Inc., USA)<br /><br />Results: Assessment using recombinant enzymes showed that mitragynine gave the strongest inhibitory effect on CYP2D6 with an IC50 value of 0.45±0.33 mM, followed by CYP2C9 and CYP3A4 with IC50 values of 9.70±4.80 and 41.32±6.74 µM respectively. Positive inhibitors appropriate for CYP2C9, CYP2D6, and CYP3A4 which are sulfaphenazole, quinidine and ketoconazole were used respectively. Vmax values of CYP2C9, CYP2D6 and CYP3A4 were 0.0005, 0.01155 and 0.0137 µM luciferin formed/pmol/min respectively. Km values of CYP2C9, CYP2D6, and CYP3A4 were 32.65, 56.01, and 103.30 µM respectively. Mitragynine noncompetitively inhibits CYP2C9 and CYP2D6 activities with the Ki values of 61.48 and 12.86 µM respectively. On the other hand, mitragynine inhibits CYP3A4 competitively with a Ki value of 379.18 µM.<br /><br />Conclusions: The findings of this study reveal that mitragynine might inhibit cytochrome P450 enzyme activities, specifically CYP2D6. Therefore, administration of mitragynine together with herbal or modern drugs which follow the same metabolic pathway may contribute to herb-drug interactions.","study.pubmedId":24174816,"study.embaseId":2013651136,"study.croIdentifier":"Centre for Drug Research, Penang","study.croInformation":"Universiti Sains Malaysia","study.dateStart":"2010-09-01T00:00:00.000Z","study.dateEnd":"2011-07-31T00:00:00.000Z","study.internalComment":null,"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":1,"cytochromeB5.name":"Co-expressed","cytochromeB5.sortOrder":1,"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":10800,"experimentAnswers.text":null,"experimentAnswers.answerId":7,"experimentAnswers.experimentId":595,"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":7,"experimentAnswers.answer.text":"NADPH regenerating system","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":595,"uid":"NPDI-ypADxQ","name":"No inhibition of CYP3A4 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>High probability of interaction if their IC50 values are less than 1 &micro;M. If IC50 values are between 1 and 10 &micro;M, they have moderate possibility in interaction. Low drug-drug interactions if their IC50 values are greater than 10 &micro;M.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"Mitragynine was isolated in-house. This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.","resultsComment":"IC50 values from Table 1, Ki values from Table 3<br /><br />% enzyme inhibition versus precipitant concentration:<br />Values estimated from Figure 2. In some cases, SEM could not be estimated from the provided figure.<br /><br />0.02 μM: -24 ± 0%<br />0.2 μM: -21 ± 5%<br />2 μM: -2 ± 1%<br />20 μM: 25 ± 2%<br />200 μM: See above data","internalComment":null,"objectCompoundId":196,"objectMetaboliteCompoundId":194,"precipitantCompoundId":94,"cytochromeB5Id":1,"studyId":128,"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":196,"objectCompound.name":"luciferin 6’benzyl ether (luciferin-be)","objectCompound.unii":null,"objectCompound.inChIKey":null,"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":94,"precipitantCompound.name":"mitragynine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"LELBFTMXCIIKKX-QVRQZEMUSA-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":194,"objectMetaboliteCompound.name":"luciferin","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":"AKA d-luciferin","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":13,"enzymes.name":"CYP3A4","enzymes.conceptId":4306811,"enzymes.experiment_enzyme_xref.enzymeId":13,"enzymes.experiment_enzyme_xref.experimentId":595,"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":128,"study.uid":"NPDI-XtvOZQ","study.name":"Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities","study.napdiIdentifier":null,"study.overallSummary":"Context: To date, many findings reveal that most of the modern drugs have the ability to interact with herbal drugs. <br /><br />Aims: This study was conducted to determine the inhibitory effects of mitragynine on cytochrome P450 2C9, 2D6 and 3A4 activities. <br /><br />Methods and Material: The in vitro study was conducted using a high-throughput luminescence assay. <br /><br />Statistical Analysis: Statistical analysis was conducted using one-way ANOVA and Dunnett's test with P &lt; 0.05 vs. control. The IC values were calculated using the GraphPad Prism 5 (Version 5.01, GraphPad Software, Inc., USA)<br /><br />Results: Assessment using recombinant enzymes showed that mitragynine gave the strongest inhibitory effect on CYP2D6 with an IC50 value of 0.45±0.33 mM, followed by CYP2C9 and CYP3A4 with IC50 values of 9.70±4.80 and 41.32±6.74 µM respectively. Positive inhibitors appropriate for CYP2C9, CYP2D6, and CYP3A4 which are sulfaphenazole, quinidine and ketoconazole were used respectively. Vmax values of CYP2C9, CYP2D6 and CYP3A4 were 0.0005, 0.01155 and 0.0137 µM luciferin formed/pmol/min respectively. Km values of CYP2C9, CYP2D6, and CYP3A4 were 32.65, 56.01, and 103.30 µM respectively. Mitragynine noncompetitively inhibits CYP2C9 and CYP2D6 activities with the Ki values of 61.48 and 12.86 µM respectively. On the other hand, mitragynine inhibits CYP3A4 competitively with a Ki value of 379.18 µM.<br /><br />Conclusions: The findings of this study reveal that mitragynine might inhibit cytochrome P450 enzyme activities, specifically CYP2D6. Therefore, administration of mitragynine together with herbal or modern drugs which follow the same metabolic pathway may contribute to herb-drug interactions.","study.pubmedId":24174816,"study.embaseId":2013651136,"study.croIdentifier":"Centre for Drug Research, Penang","study.croInformation":"Universiti Sains Malaysia","study.dateStart":"2010-09-01T00:00:00.000Z","study.dateEnd":"2011-07-31T00:00:00.000Z","study.internalComment":null,"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":1,"cytochromeB5.name":"Co-expressed","cytochromeB5.sortOrder":1,"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":10800,"experimentAnswers.text":null,"experimentAnswers.answerId":7,"experimentAnswers.experimentId":595,"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":7,"experimentAnswers.answer.text":"NADPH regenerating system","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":7},{"id":595,"uid":"NPDI-ypADxQ","name":"No inhibition of CYP3A4 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>High probability of interaction if their IC50 values are less than 1 &micro;M. If IC50 values are between 1 and 10 &micro;M, they have moderate possibility in interaction. Low drug-drug interactions if their IC50 values are greater than 10 &micro;M.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"Mitragynine was isolated in-house. This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.","resultsComment":"IC50 values from Table 1, Ki values from Table 3<br /><br />% enzyme inhibition versus precipitant concentration:<br />Values estimated from Figure 2. In some cases, SEM could not be estimated from the provided figure.<br /><br />0.02 μM: -24 ± 0%<br />0.2 μM: -21 ± 5%<br />2 μM: -2 ± 1%<br />20 μM: 25 ± 2%<br />200 μM: See above data","internalComment":null,"objectCompoundId":196,"objectMetaboliteCompoundId":194,"precipitantCompoundId":94,"cytochromeB5Id":1,"studyId":128,"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":196,"objectCompound.name":"luciferin 6’benzyl ether (luciferin-be)","objectCompound.unii":null,"objectCompound.inChIKey":null,"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":94,"precipitantCompound.name":"mitragynine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"LELBFTMXCIIKKX-QVRQZEMUSA-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":194,"objectMetaboliteCompound.name":"luciferin","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":"AKA d-luciferin","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":13,"enzymes.name":"CYP3A4","enzymes.conceptId":4306811,"enzymes.experiment_enzyme_xref.enzymeId":13,"enzymes.experiment_enzyme_xref.experimentId":595,"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":128,"study.uid":"NPDI-XtvOZQ","study.name":"Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities","study.napdiIdentifier":null,"study.overallSummary":"Context: To date, many findings reveal that most of the modern drugs have the ability to interact with herbal drugs. <br /><br />Aims: This study was conducted to determine the inhibitory effects of mitragynine on cytochrome P450 2C9, 2D6 and 3A4 activities. <br /><br />Methods and Material: The in vitro study was conducted using a high-throughput luminescence assay. <br /><br />Statistical Analysis: Statistical analysis was conducted using one-way ANOVA and Dunnett's test with P &lt; 0.05 vs. control. The IC values were calculated using the GraphPad Prism 5 (Version 5.01, GraphPad Software, Inc., USA)<br /><br />Results: Assessment using recombinant enzymes showed that mitragynine gave the strongest inhibitory effect on CYP2D6 with an IC50 value of 0.45±0.33 mM, followed by CYP2C9 and CYP3A4 with IC50 values of 9.70±4.80 and 41.32±6.74 µM respectively. Positive inhibitors appropriate for CYP2C9, CYP2D6, and CYP3A4 which are sulfaphenazole, quinidine and ketoconazole were used respectively. Vmax values of CYP2C9, CYP2D6 and CYP3A4 were 0.0005, 0.01155 and 0.0137 µM luciferin formed/pmol/min respectively. Km values of CYP2C9, CYP2D6, and CYP3A4 were 32.65, 56.01, and 103.30 µM respectively. Mitragynine noncompetitively inhibits CYP2C9 and CYP2D6 activities with the Ki values of 61.48 and 12.86 µM respectively. On the other hand, mitragynine inhibits CYP3A4 competitively with a Ki value of 379.18 µM.<br /><br />Conclusions: The findings of this study reveal that mitragynine might inhibit cytochrome P450 enzyme activities, specifically CYP2D6. Therefore, administration of mitragynine together with herbal or modern drugs which follow the same metabolic pathway may contribute to herb-drug interactions.","study.pubmedId":24174816,"study.embaseId":2013651136,"study.croIdentifier":"Centre for Drug Research, Penang","study.croInformation":"Universiti Sains Malaysia","study.dateStart":"2010-09-01T00:00:00.000Z","study.dateEnd":"2011-07-31T00:00:00.000Z","study.internalComment":null,"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":1,"cytochromeB5.name":"Co-expressed","cytochromeB5.sortOrder":1,"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":10801,"experimentAnswers.text":null,"experimentAnswers.answerId":13,"experimentAnswers.experimentId":595,"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":595,"uid":"NPDI-ypADxQ","name":"No inhibition of CYP3A4 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>High probability of interaction if their IC50 values are less than 1 &micro;M. If IC50 values are between 1 and 10 &micro;M, they have moderate possibility in interaction. Low drug-drug interactions if their IC50 values are greater than 10 &micro;M.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"Mitragynine was isolated in-house. This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.","resultsComment":"IC50 values from Table 1, Ki values from Table 3<br /><br />% enzyme inhibition versus precipitant concentration:<br />Values estimated from Figure 2. In some cases, SEM could not be estimated from the provided figure.<br /><br />0.02 μM: -24 ± 0%<br />0.2 μM: -21 ± 5%<br />2 μM: -2 ± 1%<br />20 μM: 25 ± 2%<br />200 μM: See above data","internalComment":null,"objectCompoundId":196,"objectMetaboliteCompoundId":194,"precipitantCompoundId":94,"cytochromeB5Id":1,"studyId":128,"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":196,"objectCompound.name":"luciferin 6’benzyl ether (luciferin-be)","objectCompound.unii":null,"objectCompound.inChIKey":null,"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":94,"precipitantCompound.name":"mitragynine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"LELBFTMXCIIKKX-QVRQZEMUSA-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":194,"objectMetaboliteCompound.name":"luciferin","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":"AKA d-luciferin","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":13,"enzymes.name":"CYP3A4","enzymes.conceptId":4306811,"enzymes.experiment_enzyme_xref.enzymeId":13,"enzymes.experiment_enzyme_xref.experimentId":595,"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":128,"study.uid":"NPDI-XtvOZQ","study.name":"Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities","study.napdiIdentifier":null,"study.overallSummary":"Context: To date, many findings reveal that most of the modern drugs have the ability to interact with herbal drugs. <br /><br />Aims: This study was conducted to determine the inhibitory effects of mitragynine on cytochrome P450 2C9, 2D6 and 3A4 activities. <br /><br />Methods and Material: The in vitro study was conducted using a high-throughput luminescence assay. <br /><br />Statistical Analysis: Statistical analysis was conducted using one-way ANOVA and Dunnett's test with P &lt; 0.05 vs. control. The IC values were calculated using the GraphPad Prism 5 (Version 5.01, GraphPad Software, Inc., USA)<br /><br />Results: Assessment using recombinant enzymes showed that mitragynine gave the strongest inhibitory effect on CYP2D6 with an IC50 value of 0.45±0.33 mM, followed by CYP2C9 and CYP3A4 with IC50 values of 9.70±4.80 and 41.32±6.74 µM respectively. Positive inhibitors appropriate for CYP2C9, CYP2D6, and CYP3A4 which are sulfaphenazole, quinidine and ketoconazole were used respectively. Vmax values of CYP2C9, CYP2D6 and CYP3A4 were 0.0005, 0.01155 and 0.0137 µM luciferin formed/pmol/min respectively. Km values of CYP2C9, CYP2D6, and CYP3A4 were 32.65, 56.01, and 103.30 µM respectively. Mitragynine noncompetitively inhibits CYP2C9 and CYP2D6 activities with the Ki values of 61.48 and 12.86 µM respectively. On the other hand, mitragynine inhibits CYP3A4 competitively with a Ki value of 379.18 µM.<br /><br />Conclusions: The findings of this study reveal that mitragynine might inhibit cytochrome P450 enzyme activities, specifically CYP2D6. Therefore, administration of mitragynine together with herbal or modern drugs which follow the same metabolic pathway may contribute to herb-drug interactions.","study.pubmedId":24174816,"study.embaseId":2013651136,"study.croIdentifier":"Centre for Drug Research, Penang","study.croInformation":"Universiti Sains Malaysia","study.dateStart":"2010-09-01T00:00:00.000Z","study.dateEnd":"2011-07-31T00:00:00.000Z","study.internalComment":null,"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":1,"cytochromeB5.name":"Co-expressed","cytochromeB5.sortOrder":1,"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":10801,"experimentAnswers.text":null,"experimentAnswers.answerId":13,"experimentAnswers.experimentId":595,"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":595,"uid":"NPDI-ypADxQ","name":"No inhibition of CYP3A4 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>High probability of interaction if their IC50 values are less than 1 &micro;M. If IC50 values are between 1 and 10 &micro;M, they have moderate possibility in interaction. Low drug-drug interactions if their IC50 values are greater than 10 &micro;M.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"Mitragynine was isolated in-house. This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.","resultsComment":"IC50 values from Table 1, Ki values from Table 3<br /><br />% enzyme inhibition versus precipitant concentration:<br />Values estimated from Figure 2. In some cases, SEM could not be estimated from the provided figure.<br /><br />0.02 μM: -24 ± 0%<br />0.2 μM: -21 ± 5%<br />2 μM: -2 ± 1%<br />20 μM: 25 ± 2%<br />200 μM: See above data","internalComment":null,"objectCompoundId":196,"objectMetaboliteCompoundId":194,"precipitantCompoundId":94,"cytochromeB5Id":1,"studyId":128,"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":196,"objectCompound.name":"luciferin 6’benzyl ether (luciferin-be)","objectCompound.unii":null,"objectCompound.inChIKey":null,"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":94,"precipitantCompound.name":"mitragynine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"LELBFTMXCIIKKX-QVRQZEMUSA-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":194,"objectMetaboliteCompound.name":"luciferin","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":"AKA d-luciferin","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":13,"enzymes.name":"CYP3A4","enzymes.conceptId":4306811,"enzymes.experiment_enzyme_xref.enzymeId":13,"enzymes.experiment_enzyme_xref.experimentId":595,"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":128,"study.uid":"NPDI-XtvOZQ","study.name":"Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities","study.napdiIdentifier":null,"study.overallSummary":"Context: To date, many findings reveal that most of the modern drugs have the ability to interact with herbal drugs. <br /><br />Aims: This study was conducted to determine the inhibitory effects of mitragynine on cytochrome P450 2C9, 2D6 and 3A4 activities. <br /><br />Methods and Material: The in vitro study was conducted using a high-throughput luminescence assay. <br /><br />Statistical Analysis: Statistical analysis was conducted using one-way ANOVA and Dunnett's test with P &lt; 0.05 vs. control. The IC values were calculated using the GraphPad Prism 5 (Version 5.01, GraphPad Software, Inc., USA)<br /><br />Results: Assessment using recombinant enzymes showed that mitragynine gave the strongest inhibitory effect on CYP2D6 with an IC50 value of 0.45±0.33 mM, followed by CYP2C9 and CYP3A4 with IC50 values of 9.70±4.80 and 41.32±6.74 µM respectively. Positive inhibitors appropriate for CYP2C9, CYP2D6, and CYP3A4 which are sulfaphenazole, quinidine and ketoconazole were used respectively. Vmax values of CYP2C9, CYP2D6 and CYP3A4 were 0.0005, 0.01155 and 0.0137 µM luciferin formed/pmol/min respectively. Km values of CYP2C9, CYP2D6, and CYP3A4 were 32.65, 56.01, and 103.30 µM respectively. Mitragynine noncompetitively inhibits CYP2C9 and CYP2D6 activities with the Ki values of 61.48 and 12.86 µM respectively. On the other hand, mitragynine inhibits CYP3A4 competitively with a Ki value of 379.18 µM.<br /><br />Conclusions: The findings of this study reveal that mitragynine might inhibit cytochrome P450 enzyme activities, specifically CYP2D6. Therefore, administration of mitragynine together with herbal or modern drugs which follow the same metabolic pathway may contribute to herb-drug interactions.","study.pubmedId":24174816,"study.embaseId":2013651136,"study.croIdentifier":"Centre for Drug Research, Penang","study.croInformation":"Universiti Sains Malaysia","study.dateStart":"2010-09-01T00:00:00.000Z","study.dateEnd":"2011-07-31T00:00:00.000Z","study.internalComment":null,"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":1,"cytochromeB5.name":"Co-expressed","cytochromeB5.sortOrder":1,"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":10802,"experimentAnswers.text":null,"experimentAnswers.answerId":14,"experimentAnswers.experimentId":595,"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":14,"experimentAnswers.answer.text":"Available","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":10},{"id":595,"uid":"NPDI-ypADxQ","name":"No inhibition of CYP3A4 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>High probability of interaction if their IC50 values are less than 1 &micro;M. If IC50 values are between 1 and 10 &micro;M, they have moderate possibility in interaction. Low drug-drug interactions if their IC50 values are greater than 10 &micro;M.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"Mitragynine was isolated in-house. This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.","resultsComment":"IC50 values from Table 1, Ki values from Table 3<br /><br />% enzyme inhibition versus precipitant concentration:<br />Values estimated from Figure 2. In some cases, SEM could not be estimated from the provided figure.<br /><br />0.02 μM: -24 ± 0%<br />0.2 μM: -21 ± 5%<br />2 μM: -2 ± 1%<br />20 μM: 25 ± 2%<br />200 μM: See above data","internalComment":null,"objectCompoundId":196,"objectMetaboliteCompoundId":194,"precipitantCompoundId":94,"cytochromeB5Id":1,"studyId":128,"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":196,"objectCompound.name":"luciferin 6’benzyl ether (luciferin-be)","objectCompound.unii":null,"objectCompound.inChIKey":null,"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":94,"precipitantCompound.name":"mitragynine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"LELBFTMXCIIKKX-QVRQZEMUSA-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":194,"objectMetaboliteCompound.name":"luciferin","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":"AKA d-luciferin","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":13,"enzymes.name":"CYP3A4","enzymes.conceptId":4306811,"enzymes.experiment_enzyme_xref.enzymeId":13,"enzymes.experiment_enzyme_xref.experimentId":595,"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":128,"study.uid":"NPDI-XtvOZQ","study.name":"Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities","study.napdiIdentifier":null,"study.overallSummary":"Context: To date, many findings reveal that most of the modern drugs have the ability to interact with herbal drugs. <br /><br />Aims: This study was conducted to determine the inhibitory effects of mitragynine on cytochrome P450 2C9, 2D6 and 3A4 activities. <br /><br />Methods and Material: The in vitro study was conducted using a high-throughput luminescence assay. <br /><br />Statistical Analysis: Statistical analysis was conducted using one-way ANOVA and Dunnett's test with P &lt; 0.05 vs. control. The IC values were calculated using the GraphPad Prism 5 (Version 5.01, GraphPad Software, Inc., USA)<br /><br />Results: Assessment using recombinant enzymes showed that mitragynine gave the strongest inhibitory effect on CYP2D6 with an IC50 value of 0.45±0.33 mM, followed by CYP2C9 and CYP3A4 with IC50 values of 9.70±4.80 and 41.32±6.74 µM respectively. Positive inhibitors appropriate for CYP2C9, CYP2D6, and CYP3A4 which are sulfaphenazole, quinidine and ketoconazole were used respectively. Vmax values of CYP2C9, CYP2D6 and CYP3A4 were 0.0005, 0.01155 and 0.0137 µM luciferin formed/pmol/min respectively. Km values of CYP2C9, CYP2D6, and CYP3A4 were 32.65, 56.01, and 103.30 µM respectively. Mitragynine noncompetitively inhibits CYP2C9 and CYP2D6 activities with the Ki values of 61.48 and 12.86 µM respectively. On the other hand, mitragynine inhibits CYP3A4 competitively with a Ki value of 379.18 µM.<br /><br />Conclusions: The findings of this study reveal that mitragynine might inhibit cytochrome P450 enzyme activities, specifically CYP2D6. Therefore, administration of mitragynine together with herbal or modern drugs which follow the same metabolic pathway may contribute to herb-drug interactions.","study.pubmedId":24174816,"study.embaseId":2013651136,"study.croIdentifier":"Centre for Drug Research, Penang","study.croInformation":"Universiti Sains Malaysia","study.dateStart":"2010-09-01T00:00:00.000Z","study.dateEnd":"2011-07-31T00:00:00.000Z","study.internalComment":null,"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":1,"cytochromeB5.name":"Co-expressed","cytochromeB5.sortOrder":1,"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":10802,"experimentAnswers.text":null,"experimentAnswers.answerId":14,"experimentAnswers.experimentId":595,"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":14,"experimentAnswers.answer.text":"Available","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":10},{"id":595,"uid":"NPDI-ypADxQ","name":"No inhibition of CYP3A4 by mitragynine","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>High probability of interaction if their IC50 values are less than 1 &micro;M. If IC50 values are between 1 and 10 &micro;M, they have moderate possibility in interaction. Low drug-drug interactions if their IC50 values are greater than 10 &micro;M.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"Mitragynine was isolated in-house. This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.","resultsComment":"IC50 values from Table 1, Ki values from Table 3<br /><br />% enzyme inhibition versus precipitant concentration:<br />Values estimated from Figure 2. In some cases, SEM could not be estimated from the provided figure.<br /><br />0.02 μM: -24 ± 0%<br />0.2 μM: -21 ± 5%<br />2 μM: -2 ± 1%<br />20 μM: 25 ± 2%<br />200 μM: See above data","internalComment":null,"objectCompoundId":196,"objectMetaboliteCompoundId":194,"precipitantCompoundId":94,"cytochromeB5Id":1,"studyId":128,"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":196,"objectCompound.name":"luciferin 6’benzyl ether (luciferin-be)","objectCompound.unii":null,"objectCompound.inChIKey":null,"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":94,"precipitantCompound.name":"mitragynine","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"LELBFTMXCIIKKX-QVRQZEMUSA-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":194,"objectMetaboliteCompound.name":"luciferin","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":"AKA d-luciferin","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":13,"enzymes.name":"CYP3A4","enzymes.conceptId":4306811,"enzymes.experiment_enzyme_xref.enzymeId":13,"enzymes.experiment_enzyme_xref.experimentId":595,"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":128,"study.uid":"NPDI-XtvOZQ","study.name":"Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities","study.napdiIdentifier":null,"study.overallSummary":"Context: To date, many findings reveal that most of the modern drugs have the ability to interact with herbal drugs. <br /><br />Aims: This study was conducted to determine the inhibitory effects of mitragynine on cytochrome P450 2C9, 2D6 and 3A4 activities. <br /><br />Methods and Material: The in vitro study was conducted using a high-throughput luminescence assay. <br /><br />Statistical Analysis: Statistical analysis was conducted using one-way ANOVA and Dunnett's test with P &lt; 0.05 vs. control. The IC values were calculated using the GraphPad Prism 5 (Version 5.01, GraphPad Software, Inc., USA)<br /><br />Results: Assessment using recombinant enzymes showed that mitragynine gave the strongest inhibitory effect on CYP2D6 with an IC50 value of 0.45±0.33 mM, followed by CYP2C9 and CYP3A4 with IC50 values of 9.70±4.80 and 41.32±6.74 µM respectively. Positive inhibitors appropriate for CYP2C9, CYP2D6, and CYP3A4 which are sulfaphenazole, quinidine and ketoconazole were used respectively. Vmax values of CYP2C9, CYP2D6 and CYP3A4 were 0.0005, 0.01155 and 0.0137 µM luciferin formed/pmol/min respectively. Km values of CYP2C9, CYP2D6, and CYP3A4 were 32.65, 56.01, and 103.30 µM respectively. Mitragynine noncompetitively inhibits CYP2C9 and CYP2D6 activities with the Ki values of 61.48 and 12.86 µM respectively. On the other hand, mitragynine inhibits CYP3A4 competitively with a Ki value of 379.18 µM.<br /><br />Conclusions: The findings of this study reveal that mitragynine might inhibit cytochrome P450 enzyme activities, specifically CYP2D6. Therefore, administration of mitragynine together with herbal or modern drugs which follow the same metabolic pathway may contribute to herb-drug interactions.","study.pubmedId":24174816,"study.embaseId":2013651136,"study.croIdentifier":"Centre for Drug Research, Penang","study.croInformation":"Universiti Sains Malaysia","study.dateStart":"2010-09-01T00:00:00.000Z","study.dateEnd":"2011-07-31T00:00:00.000Z","study.internalComment":null,"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":1,"cytochromeB5.name":"Co-expressed","cytochromeB5.sortOrder":1,"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":10803,"experimentAnswers.text":"0.02-200 µM","experimentAnswers.answerId":null,"experimentAnswers.experimentId":595,"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}]