{"id":"1c959b0f-c2e8-5763-ac94-687168d28b7d","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-cyp2c8-metabolite","predicate":"reversibly_inhibits","statement":"Geraldol reversibly and noncompetitively inhibited CYP2C8-mediated paclitaxel hydroxylation in human liver microsomes, with reported Ki 11.5 micromolar.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"9659b4a1-23d9-5e5e-b449-f2ebb6cb27e3","mechanism_event_label":"The parent and metabolite can affect the same drug-metabolizing enzyme.","subject":{"id":"9fdb2610-ab87-5de2-9658-ed83bc42b3fc","slug":"geraldol","display_name":"Geraldol / 3-prime-O-methylfisetin","entity_type_key":"small_molecule"},"object":{"id":"eb6d83d8-65fd-5cb0-a8e2-b0bb74506200","slug":"cyp2c8","display_name":"Human cytochrome P450 2C8","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"9659b4a1-23d9-5e5e-b449-f2ebb6cb27e3","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-cyp2c8-metabolite-event","event_type":"observed_relationship","label":"The parent and metabolite can affect the same drug-metabolizing enzyme.","description":"Geraldol reversibly and noncompetitively inhibited CYP2C8-mediated paclitaxel hydroxylation in human liver microsomes, with reported Ki 11.5 micromolar.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9fdb2610-ab87-5de2-9658-ed83bc42b3fc","slug":"geraldol","display_name":"Geraldol / 3-prime-O-methylfisetin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"eb6d83d8-65fd-5cb0-a8e2-b0bb74506200","slug":"cyp2c8","display_name":"Human cytochrome P450 2C8","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"dee05061-c3f3-5226-8054-dd58b76a585d","slug":"fisetin","display_name":"Fisetin","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"0727cb60-dd74-52d0-ac12-86697e75ac71","slug":"paclitaxel","display_name":"Paclitaxel","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Pooled human liver microsomes; preincubation and kinetic comparisons.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"In vitro hazard signal; no measured clinical drug-exposure change or dosing adjustment follows.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"fisetin","display_name":"Fisetin","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"The parent and metabolite can affect the same drug-metabolizing enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Selective inhibition of CYP2C8 by fisetin and its methylated metabolite, geraldol, in human liver microsomes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29454704/ · DOI 10.1016/j.dmpk.2017.12.006","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"83155749-1c3e-5d11-9c71-ea15b2e4635e","evidence_kind":"source_excerpt","locator":"Lines 472-478","start_line":472,"end_line":478,"excerpt":"## fisetin-cyp2c8-metabolite\nThe parent and metabolite can affect the same drug-metabolizing enzyme.\nGeraldol reversibly and noncompetitively inhibited CYP2C8-mediated paclitaxel hydroxylation in human liver microsomes, with reported Ki 11.5 micromolar.\nModel: Pooled human liver microsomes; preincubation and kinetic comparisons.\nLimitations: In vitro hazard signal; no measured clinical drug-exposure change or dosing adjustment follows.\nEvidence access: Primary abstract\nSelective inhibition of CYP2C8 by fisetin and its methylated metabolite, geraldol, in human liver microsomes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29454704/ · DOI 10.1016/j.dmpk.2017.12.006","model_system":"Pooled human liver microsomes; preincubation and kinetic comparisons.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"1108bfff-6504-5152-a51f-ff3d7c27c282","stable_key":"import-74ef5bba-ee14-531c-b1bf-d1f297c56bb6","title":"Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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