{"id":"b0e94185-d0d6-5cf0-b1cd-4bd5c60f9793","stable_key":"1bbf9d44-8d2b-5b35-8f82-f6876558b0b3:human-kidney-microsomes-form-am9","predicate":"produces","statement":"Microsomes from human kidney produced only AM9, and the rate of formation at 2 and 20 micromolar cyclosporine was positively associated with detectable CYP3A5 protein and with the CYP3A5*1 allele in 4 of the 20 kidneys tested.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"030870b2-de8a-51df-8c4a-2cd7b5ceb04b","mechanism_event_label":"Microsomes from human kidney produced only AM9, and the rate of formation at 2 and 20 micromolar cyclosporine was positively associated with detectable CYP3A5 protein and with the CYP3A5*1 allele in 4","subject":{"id":"738a35b4-fde1-5898-a6a2-a4a469c61822","slug":"human-kidney-microsomal-cyp3a","display_name":"Human kidney microsomal CYP3A activity, twenty-donor panel","entity_type_key":"protein_set"},"object":{"id":"88cbe0fd-1485-59f3-b99d-a2b314fee751","slug":"cyclosporine-am9","display_name":"Cyclosporine metabolite AM9","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"030870b2-de8a-51df-8c4a-2cd7b5ceb04b","stable_key":"1bbf9d44-8d2b-5b35-8f82-f6876558b0b3:human-kidney-microsomes-form-am9-event","event_type":"biochemical_relationship","label":"Microsomes from human kidney produced only AM9, and the rate of formation at 2 and 20 micromolar cyclosporine was positively associated with detectable CYP3A5 protein and with the CYP3A5*1 allele in 4","description":"Renal drug metabolism","status":"provisional","compartment":null,"participants":[{"entity":{"id":"738a35b4-fde1-5898-a6a2-a4a469c61822","slug":"human-kidney-microsomal-cyp3a","display_name":"Human kidney microsomal CYP3A activity, twenty-donor panel","entity_type_key":"protein_set"},"role":"acting component","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"88cbe0fd-1485-59f3-b99d-a2b314fee751","slug":"cyclosporine-am9","display_name":"Cyclosporine metabolite AM9","entity_type_key":"small_molecule"},"role":"component the finding is about","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Not stated here","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary PubMed abstract and indexed metadata reviewed. 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Ketoconazole at 200 nanomolar inhibited renal AM9 formation by 22 to 55 per cent across 2 to 45 micromolar cyclosporine, which supports a CYP3A route without isolating CYP3A5 from CYP3A4 pharmacologically.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Human kidney microsomes from twenty donors","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Microsomes from human kidney produced only AM9, and the rate of formation at 2 and 20 micromolar cyclosporine was positively associated with detectable CYP3A5 protein and with the CYP3A5*1 allele in 4 of the 20 kidneys tested.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"In vitro metabolism of cyclosporine A by human kidney CYP3A5. 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No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text.","file_path":"","sha256":"499d00555a629cba2271c3888d7e93627949891d565c4c78c843610de2913080","revision_id":"263ee68a-4184-51d0-a977-197d7ddb7a4d","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}