{"id":"cc44417f-6724-5cc3-b057-1f4e51c22654","stable_key":"1bbf9d44-8d2b-5b35-8f82-f6876558b0b3:cyp3a4-metabolises-cyclosporine","predicate":"metabolizes","statement":"Heterologously expressed CYP3A4 produced three primary cyclosporine metabolites, AM1, AM9 and AM4N, with substrate inhibition observed for AM1 and AM9 formation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"60a1959d-1899-56bc-8b3f-82489f21f2d5","mechanism_event_label":"Heterologously expressed CYP3A4 produced three primary cyclosporine metabolites, AM1, AM9 and AM4N, with substrate inhibition observed for AM1 and AM9 formation.","subject":{"id":"54e95ff1-4ffa-5e6f-a4cb-b47e5d2a5bda","slug":"cyp3a4","display_name":"Human cytochrome P450 3A4","entity_type_key":"protein"},"object":{"id":"b199063a-fae6-5c5c-9cb4-22c10453bbac","slug":"cyclosporine","display_name":"Cyclosporine","entity_type_key":"drug"},"evidence_count":1,"mechanism_event":{"id":"60a1959d-1899-56bc-8b3f-82489f21f2d5","stable_key":"1bbf9d44-8d2b-5b35-8f82-f6876558b0b3:cyp3a4-metabolises-cyclosporine-event","event_type":"biochemical_relationship","label":"Heterologously expressed CYP3A4 produced three primary cyclosporine metabolites, AM1, AM9 and AM4N, with substrate inhibition observed for AM1 and AM9 formation.","description":"Oxidative drug metabolism","status":"provisional","compartment":null,"participants":[{"entity":{"id":"54e95ff1-4ffa-5e6f-a4cb-b47e5d2a5bda","slug":"cyp3a4","display_name":"Human cytochrome P450 3A4","entity_type_key":"protein"},"role":"acting component","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b199063a-fae6-5c5c-9cb4-22c10453bbac","slug":"cyclosporine","display_name":"Cyclosporine","entity_type_key":"drug"},"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. Full-text method details not stated here remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Heterologously expressed human CYP3A4","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Cyclosporin A","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Substrate inhibition means the rate does not rise linearly with concentration, so a single-point rate from this system does not scale. 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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}