[{"id":930,"uid":"NPDI-LI0O-A","name":"Inhibition of CES1 by CBN","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"
90% inhibition
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"Table 2","internalComment":null,"objectCompoundId":268,"objectMetaboliteCompoundId":278,"precipitantCompoundId":153,"cytochromeB5Id":null,"studyId":187,"experimentTypeId":1,"testSystemId":44,"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":268,"objectCompound.name":"oseltamivir phosphate","objectCompound.unii":null,"objectCompound.inChIKey":"PGZUMBJQJWIWGJ-ONAKXNSWSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":153,"precipitantCompound.name":"cannabinol","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"VBGLYOIFKLUMQG-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":278,"objectMetaboliteCompound.name":"oseltamivir acid","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"NENPYTRHICXVCS-YNEHKIRRSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":35,"enzymes.name":"CES1","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":35,"enzymes.experiment_enzyme_xref.experimentId":930,"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":187,"study.uid":"NPDI-d4aGfw","study.name":"In Vitro Inhibition of Carboxylesterase 1 by Major Cannabinoids and Selected Metabolites","study.napdiIdentifier":null,"study.overallSummary":"The escalating use of medical cannabis and significant recreational use of cannabis in recent years has led to a higher potential for metabolic interactions between cannabis or one or more of its components and concurrently used medications. Although there have been a significant number of in vitro and in vivo assessments of the effects of cannabis on cytochrome P450 and UDP-glucuronosyltransferase enzyme systems, there is limited information regarding the effects of cannabis on the major hepatic esterase, carboxylesterase 1 (CES1). In this study, we investigated the in vitro inhibitory effects of the individual major cannabinoids and metabolites Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), 11-nor-THC-carboxylic acid, and 11-hydroxy-THC on CES1 activity. S9 fractions from human embryonic kidney 293 cells stably expressing CES1 were used in the assessment of cannabinoid inhibitory effects. THC, CBD, and CBN each exhibited substantial inhibitory potency, and were further studied to determine their mechanism of inhibition and kinetic parameters. The inhibition of CES1 by THC, CBD, and CBN was reversible and appears to proceed through a mixed competitivenoncompetitive mechanism. The inhibition constant (Ki) values for THC, CBD, and CBN inhibition were 0.541, 0.974, and 0.263 mM (0.170, 0.306, and 0.0817 mg/ml), respectively. Inhibition potency was increased when THC, CBD, and CBN were combined. Compared with the potential unbound plasma concentrations attainable clinically, the Ki values suggest a potential for clinically significant inhibition of CES1 by THC and CBD. CBN, however, is expected to have a limited impact on CES1. Carefully designed clinical studies are warranted to establish the clinical significance of these in vitro findings.","study.pubmedId":30833288,"study.embaseId":null,"study.croIdentifier":"UF","study.croInformation":"University of Florida","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","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":44,"testSystem.name":"Human kidney S9 fraction","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":2,"testSystem.category.id":2,"testSystem.category.name":"Cell fraction","testSystem.category.sortOrder":2,"testSystem.category.requiresCytochromeB5":false,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"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":15821,"experimentAnswers.text":"15 min","experimentAnswers.answerId":null,"experimentAnswers.experimentId":930,"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":930,"uid":"NPDI-LI0O-A","name":"Inhibition of CES1 by CBN","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"90% inhibition
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"Table 2","internalComment":null,"objectCompoundId":268,"objectMetaboliteCompoundId":278,"precipitantCompoundId":153,"cytochromeB5Id":null,"studyId":187,"experimentTypeId":1,"testSystemId":44,"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":268,"objectCompound.name":"oseltamivir phosphate","objectCompound.unii":null,"objectCompound.inChIKey":"PGZUMBJQJWIWGJ-ONAKXNSWSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":153,"precipitantCompound.name":"cannabinol","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"VBGLYOIFKLUMQG-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":278,"objectMetaboliteCompound.name":"oseltamivir acid","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"NENPYTRHICXVCS-YNEHKIRRSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":35,"enzymes.name":"CES1","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":35,"enzymes.experiment_enzyme_xref.experimentId":930,"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":187,"study.uid":"NPDI-d4aGfw","study.name":"In Vitro Inhibition of Carboxylesterase 1 by Major Cannabinoids and Selected Metabolites","study.napdiIdentifier":null,"study.overallSummary":"The escalating use of medical cannabis and significant recreational use of cannabis in recent years has led to a higher potential for metabolic interactions between cannabis or one or more of its components and concurrently used medications. Although there have been a significant number of in vitro and in vivo assessments of the effects of cannabis on cytochrome P450 and UDP-glucuronosyltransferase enzyme systems, there is limited information regarding the effects of cannabis on the major hepatic esterase, carboxylesterase 1 (CES1). In this study, we investigated the in vitro inhibitory effects of the individual major cannabinoids and metabolites Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), 11-nor-THC-carboxylic acid, and 11-hydroxy-THC on CES1 activity. S9 fractions from human embryonic kidney 293 cells stably expressing CES1 were used in the assessment of cannabinoid inhibitory effects. THC, CBD, and CBN each exhibited substantial inhibitory potency, and were further studied to determine their mechanism of inhibition and kinetic parameters. The inhibition of CES1 by THC, CBD, and CBN was reversible and appears to proceed through a mixed competitivenoncompetitive mechanism. The inhibition constant (Ki) values for THC, CBD, and CBN inhibition were 0.541, 0.974, and 0.263 mM (0.170, 0.306, and 0.0817 mg/ml), respectively. Inhibition potency was increased when THC, CBD, and CBN were combined. Compared with the potential unbound plasma concentrations attainable clinically, the Ki values suggest a potential for clinically significant inhibition of CES1 by THC and CBD. CBN, however, is expected to have a limited impact on CES1. Carefully designed clinical studies are warranted to establish the clinical significance of these in vitro findings.","study.pubmedId":30833288,"study.embaseId":null,"study.croIdentifier":"UF","study.croInformation":"University of Florida","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","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":44,"testSystem.name":"Human kidney S9 fraction","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":2,"testSystem.category.id":2,"testSystem.category.name":"Cell fraction","testSystem.category.sortOrder":2,"testSystem.category.requiresCytochromeB5":false,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"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":15820,"experimentAnswers.text":"100 µL","experimentAnswers.answerId":null,"experimentAnswers.experimentId":930,"experimentAnswers.questionId":5,"experimentAnswers.question.id":5,"experimentAnswers.question.text":"Incubation volume","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":930,"uid":"NPDI-LI0O-A","name":"Inhibition of CES1 by CBN","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"90% inhibition
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"Table 2","internalComment":null,"objectCompoundId":268,"objectMetaboliteCompoundId":278,"precipitantCompoundId":153,"cytochromeB5Id":null,"studyId":187,"experimentTypeId":1,"testSystemId":44,"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":268,"objectCompound.name":"oseltamivir phosphate","objectCompound.unii":null,"objectCompound.inChIKey":"PGZUMBJQJWIWGJ-ONAKXNSWSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":153,"precipitantCompound.name":"cannabinol","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"VBGLYOIFKLUMQG-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":278,"objectMetaboliteCompound.name":"oseltamivir acid","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"NENPYTRHICXVCS-YNEHKIRRSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":35,"enzymes.name":"CES1","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":35,"enzymes.experiment_enzyme_xref.experimentId":930,"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":187,"study.uid":"NPDI-d4aGfw","study.name":"In Vitro Inhibition of Carboxylesterase 1 by Major Cannabinoids and Selected Metabolites","study.napdiIdentifier":null,"study.overallSummary":"The escalating use of medical cannabis and significant recreational use of cannabis in recent years has led to a higher potential for metabolic interactions between cannabis or one or more of its components and concurrently used medications. Although there have been a significant number of in vitro and in vivo assessments of the effects of cannabis on cytochrome P450 and UDP-glucuronosyltransferase enzyme systems, there is limited information regarding the effects of cannabis on the major hepatic esterase, carboxylesterase 1 (CES1). In this study, we investigated the in vitro inhibitory effects of the individual major cannabinoids and metabolites Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), 11-nor-THC-carboxylic acid, and 11-hydroxy-THC on CES1 activity. S9 fractions from human embryonic kidney 293 cells stably expressing CES1 were used in the assessment of cannabinoid inhibitory effects. THC, CBD, and CBN each exhibited substantial inhibitory potency, and were further studied to determine their mechanism of inhibition and kinetic parameters. The inhibition of CES1 by THC, CBD, and CBN was reversible and appears to proceed through a mixed competitivenoncompetitive mechanism. The inhibition constant (Ki) values for THC, CBD, and CBN inhibition were 0.541, 0.974, and 0.263 mM (0.170, 0.306, and 0.0817 mg/ml), respectively. Inhibition potency was increased when THC, CBD, and CBN were combined. Compared with the potential unbound plasma concentrations attainable clinically, the Ki values suggest a potential for clinically significant inhibition of CES1 by THC and CBD. CBN, however, is expected to have a limited impact on CES1. Carefully designed clinical studies are warranted to establish the clinical significance of these in vitro findings.","study.pubmedId":30833288,"study.embaseId":null,"study.croIdentifier":"UF","study.croInformation":"University of Florida","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","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":44,"testSystem.name":"Human kidney S9 fraction","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":2,"testSystem.category.id":2,"testSystem.category.name":"Cell fraction","testSystem.category.sortOrder":2,"testSystem.category.requiresCytochromeB5":false,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"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":15823,"experimentAnswers.text":"0 - 10 µg/mL","experimentAnswers.answerId":null,"experimentAnswers.experimentId":930,"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},{"id":930,"uid":"NPDI-LI0O-A","name":"Inhibition of CES1 by CBN","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"90% inhibition
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"Table 2","internalComment":null,"objectCompoundId":268,"objectMetaboliteCompoundId":278,"precipitantCompoundId":153,"cytochromeB5Id":null,"studyId":187,"experimentTypeId":1,"testSystemId":44,"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":268,"objectCompound.name":"oseltamivir phosphate","objectCompound.unii":null,"objectCompound.inChIKey":"PGZUMBJQJWIWGJ-ONAKXNSWSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":153,"precipitantCompound.name":"cannabinol","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"VBGLYOIFKLUMQG-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":278,"objectMetaboliteCompound.name":"oseltamivir acid","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"NENPYTRHICXVCS-YNEHKIRRSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":35,"enzymes.name":"CES1","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":35,"enzymes.experiment_enzyme_xref.experimentId":930,"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":187,"study.uid":"NPDI-d4aGfw","study.name":"In Vitro Inhibition of Carboxylesterase 1 by Major Cannabinoids and Selected Metabolites","study.napdiIdentifier":null,"study.overallSummary":"The escalating use of medical cannabis and significant recreational use of cannabis in recent years has led to a higher potential for metabolic interactions between cannabis or one or more of its components and concurrently used medications. Although there have been a significant number of in vitro and in vivo assessments of the effects of cannabis on cytochrome P450 and UDP-glucuronosyltransferase enzyme systems, there is limited information regarding the effects of cannabis on the major hepatic esterase, carboxylesterase 1 (CES1). In this study, we investigated the in vitro inhibitory effects of the individual major cannabinoids and metabolites Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), 11-nor-THC-carboxylic acid, and 11-hydroxy-THC on CES1 activity. S9 fractions from human embryonic kidney 293 cells stably expressing CES1 were used in the assessment of cannabinoid inhibitory effects. THC, CBD, and CBN each exhibited substantial inhibitory potency, and were further studied to determine their mechanism of inhibition and kinetic parameters. The inhibition of CES1 by THC, CBD, and CBN was reversible and appears to proceed through a mixed competitivenoncompetitive mechanism. The inhibition constant (Ki) values for THC, CBD, and CBN inhibition were 0.541, 0.974, and 0.263 mM (0.170, 0.306, and 0.0817 mg/ml), respectively. Inhibition potency was increased when THC, CBD, and CBN were combined. Compared with the potential unbound plasma concentrations attainable clinically, the Ki values suggest a potential for clinically significant inhibition of CES1 by THC and CBD. CBN, however, is expected to have a limited impact on CES1. Carefully designed clinical studies are warranted to establish the clinical significance of these in vitro findings.","study.pubmedId":30833288,"study.embaseId":null,"study.croIdentifier":"UF","study.croInformation":"University of Florida","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","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":44,"testSystem.name":"Human kidney S9 fraction","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":2,"testSystem.category.id":2,"testSystem.category.name":"Cell fraction","testSystem.category.sortOrder":2,"testSystem.category.requiresCytochromeB5":false,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"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":15819,"experimentAnswers.text":"20 microG/ml","experimentAnswers.answerId":null,"experimentAnswers.experimentId":930,"experimentAnswers.questionId":2,"experimentAnswers.question.id":2,"experimentAnswers.question.text":"Protein concentration","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":930,"uid":"NPDI-LI0O-A","name":"Inhibition of CES1 by CBN","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"90% inhibition
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"Table 2","internalComment":null,"objectCompoundId":268,"objectMetaboliteCompoundId":278,"precipitantCompoundId":153,"cytochromeB5Id":null,"studyId":187,"experimentTypeId":1,"testSystemId":44,"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":268,"objectCompound.name":"oseltamivir phosphate","objectCompound.unii":null,"objectCompound.inChIKey":"PGZUMBJQJWIWGJ-ONAKXNSWSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":153,"precipitantCompound.name":"cannabinol","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"VBGLYOIFKLUMQG-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":278,"objectMetaboliteCompound.name":"oseltamivir acid","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"NENPYTRHICXVCS-YNEHKIRRSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":35,"enzymes.name":"CES1","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":35,"enzymes.experiment_enzyme_xref.experimentId":930,"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":187,"study.uid":"NPDI-d4aGfw","study.name":"In Vitro Inhibition of Carboxylesterase 1 by Major Cannabinoids and Selected Metabolites","study.napdiIdentifier":null,"study.overallSummary":"The escalating use of medical cannabis and significant recreational use of cannabis in recent years has led to a higher potential for metabolic interactions between cannabis or one or more of its components and concurrently used medications. Although there have been a significant number of in vitro and in vivo assessments of the effects of cannabis on cytochrome P450 and UDP-glucuronosyltransferase enzyme systems, there is limited information regarding the effects of cannabis on the major hepatic esterase, carboxylesterase 1 (CES1). In this study, we investigated the in vitro inhibitory effects of the individual major cannabinoids and metabolites Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), 11-nor-THC-carboxylic acid, and 11-hydroxy-THC on CES1 activity. S9 fractions from human embryonic kidney 293 cells stably expressing CES1 were used in the assessment of cannabinoid inhibitory effects. THC, CBD, and CBN each exhibited substantial inhibitory potency, and were further studied to determine their mechanism of inhibition and kinetic parameters. The inhibition of CES1 by THC, CBD, and CBN was reversible and appears to proceed through a mixed competitivenoncompetitive mechanism. The inhibition constant (Ki) values for THC, CBD, and CBN inhibition were 0.541, 0.974, and 0.263 mM (0.170, 0.306, and 0.0817 mg/ml), respectively. Inhibition potency was increased when THC, CBD, and CBN were combined. Compared with the potential unbound plasma concentrations attainable clinically, the Ki values suggest a potential for clinically significant inhibition of CES1 by THC and CBD. CBN, however, is expected to have a limited impact on CES1. Carefully designed clinical studies are warranted to establish the clinical significance of these in vitro findings.","study.pubmedId":30833288,"study.embaseId":null,"study.croIdentifier":"UF","study.croInformation":"University of Florida","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","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":44,"testSystem.name":"Human kidney S9 fraction","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":2,"testSystem.category.id":2,"testSystem.category.name":"Cell fraction","testSystem.category.sortOrder":2,"testSystem.category.requiresCytochromeB5":false,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"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":15822,"experimentAnswers.text":"0, 100, 500, 1000, 2500, 5000 µM","experimentAnswers.answerId":null,"experimentAnswers.experimentId":930,"experimentAnswers.questionId":11,"experimentAnswers.question.id":11,"experimentAnswers.question.text":"Object concentrations tested","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":930,"uid":"NPDI-LI0O-A","name":"Inhibition of CES1 by CBN","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"90% inhibition
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"Table 2","internalComment":null,"objectCompoundId":268,"objectMetaboliteCompoundId":278,"precipitantCompoundId":153,"cytochromeB5Id":null,"studyId":187,"experimentTypeId":1,"testSystemId":44,"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":268,"objectCompound.name":"oseltamivir phosphate","objectCompound.unii":null,"objectCompound.inChIKey":"PGZUMBJQJWIWGJ-ONAKXNSWSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":153,"precipitantCompound.name":"cannabinol","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"VBGLYOIFKLUMQG-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":278,"objectMetaboliteCompound.name":"oseltamivir acid","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"NENPYTRHICXVCS-YNEHKIRRSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":35,"enzymes.name":"CES1","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":35,"enzymes.experiment_enzyme_xref.experimentId":930,"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":187,"study.uid":"NPDI-d4aGfw","study.name":"In Vitro Inhibition of Carboxylesterase 1 by Major Cannabinoids and Selected Metabolites","study.napdiIdentifier":null,"study.overallSummary":"The escalating use of medical cannabis and significant recreational use of cannabis in recent years has led to a higher potential for metabolic interactions between cannabis or one or more of its components and concurrently used medications. Although there have been a significant number of in vitro and in vivo assessments of the effects of cannabis on cytochrome P450 and UDP-glucuronosyltransferase enzyme systems, there is limited information regarding the effects of cannabis on the major hepatic esterase, carboxylesterase 1 (CES1). In this study, we investigated the in vitro inhibitory effects of the individual major cannabinoids and metabolites Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), 11-nor-THC-carboxylic acid, and 11-hydroxy-THC on CES1 activity. S9 fractions from human embryonic kidney 293 cells stably expressing CES1 were used in the assessment of cannabinoid inhibitory effects. THC, CBD, and CBN each exhibited substantial inhibitory potency, and were further studied to determine their mechanism of inhibition and kinetic parameters. The inhibition of CES1 by THC, CBD, and CBN was reversible and appears to proceed through a mixed competitivenoncompetitive mechanism. The inhibition constant (Ki) values for THC, CBD, and CBN inhibition were 0.541, 0.974, and 0.263 mM (0.170, 0.306, and 0.0817 mg/ml), respectively. Inhibition potency was increased when THC, CBD, and CBN were combined. Compared with the potential unbound plasma concentrations attainable clinically, the Ki values suggest a potential for clinically significant inhibition of CES1 by THC and CBD. CBN, however, is expected to have a limited impact on CES1. Carefully designed clinical studies are warranted to establish the clinical significance of these in vitro findings.","study.pubmedId":30833288,"study.embaseId":null,"study.croIdentifier":"UF","study.croInformation":"University of Florida","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","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":44,"testSystem.name":"Human kidney S9 fraction","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":2,"testSystem.category.id":2,"testSystem.category.name":"Cell fraction","testSystem.category.sortOrder":2,"testSystem.category.requiresCytochromeB5":false,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"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":15818,"experimentAnswers.text":null,"experimentAnswers.answerId":1,"experimentAnswers.experimentId":930,"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":930,"uid":"NPDI-LI0O-A","name":"Inhibition of CES1 by CBN","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"90% inhibition
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"Table 2","internalComment":null,"objectCompoundId":268,"objectMetaboliteCompoundId":278,"precipitantCompoundId":153,"cytochromeB5Id":null,"studyId":187,"experimentTypeId":1,"testSystemId":44,"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":268,"objectCompound.name":"oseltamivir phosphate","objectCompound.unii":null,"objectCompound.inChIKey":"PGZUMBJQJWIWGJ-ONAKXNSWSA-N","objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":153,"precipitantCompound.name":"cannabinol","precipitantCompound.unii":null,"precipitantCompound.inChIKey":"VBGLYOIFKLUMQG-UHFFFAOYSA-N","precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":278,"objectMetaboliteCompound.name":"oseltamivir acid","objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":"NENPYTRHICXVCS-YNEHKIRRSA-N","objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":35,"enzymes.name":"CES1","enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":35,"enzymes.experiment_enzyme_xref.experimentId":930,"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":187,"study.uid":"NPDI-d4aGfw","study.name":"In Vitro Inhibition of Carboxylesterase 1 by Major Cannabinoids and Selected Metabolites","study.napdiIdentifier":null,"study.overallSummary":"The escalating use of medical cannabis and significant recreational use of cannabis in recent years has led to a higher potential for metabolic interactions between cannabis or one or more of its components and concurrently used medications. Although there have been a significant number of in vitro and in vivo assessments of the effects of cannabis on cytochrome P450 and UDP-glucuronosyltransferase enzyme systems, there is limited information regarding the effects of cannabis on the major hepatic esterase, carboxylesterase 1 (CES1). In this study, we investigated the in vitro inhibitory effects of the individual major cannabinoids and metabolites Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), 11-nor-THC-carboxylic acid, and 11-hydroxy-THC on CES1 activity. S9 fractions from human embryonic kidney 293 cells stably expressing CES1 were used in the assessment of cannabinoid inhibitory effects. THC, CBD, and CBN each exhibited substantial inhibitory potency, and were further studied to determine their mechanism of inhibition and kinetic parameters. The inhibition of CES1 by THC, CBD, and CBN was reversible and appears to proceed through a mixed competitivenoncompetitive mechanism. The inhibition constant (Ki) values for THC, CBD, and CBN inhibition were 0.541, 0.974, and 0.263 mM (0.170, 0.306, and 0.0817 mg/ml), respectively. Inhibition potency was increased when THC, CBD, and CBN were combined. Compared with the potential unbound plasma concentrations attainable clinically, the Ki values suggest a potential for clinically significant inhibition of CES1 by THC and CBD. CBN, however, is expected to have a limited impact on CES1. Carefully designed clinical studies are warranted to establish the clinical significance of these in vitro findings.","study.pubmedId":30833288,"study.embaseId":null,"study.croIdentifier":"UF","study.croInformation":"University of Florida","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","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":44,"testSystem.name":"Human kidney S9 fraction","testSystem.sortOrder":0,"testSystem.conceptId":null,"testSystem.categoryId":2,"testSystem.category.id":2,"testSystem.category.name":"Cell fraction","testSystem.category.sortOrder":2,"testSystem.category.requiresCytochromeB5":false,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"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":15818,"experimentAnswers.text":null,"experimentAnswers.answerId":1,"experimentAnswers.experimentId":930,"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}]