{"id":"2a3854c4-f35a-5ede-893b-22643ba6ba8f","stable_key":"f812c44f-d0fd-5f01-ba2c-748c0794fcfb:coumarin-methoxsalen-inactivation","predicate":"inactivates","statement":"Methoxsalen produced mechanism-based CYP2A6 inhibition, with reported inactivation rate 0.5/min.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"20cc0ee0-5e2e-5faa-9d82-16e5ade018c9","mechanism_event_label":"Methoxsalen can disable this enzyme during metabolism.","subject":{"id":"3221abe0-7cbd-5889-a2bf-7ba8e56567a2","slug":"methoxsalen","display_name":"Methoxsalen / 8-methoxypsoralen","entity_type_key":"small_molecule"},"object":{"id":"44b7b150-3615-5d52-9db8-beb212fc31eb","slug":"cyp2a6","display_name":"Human cytochrome P450 2A6 / CYP2A6","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"20cc0ee0-5e2e-5faa-9d82-16e5ade018c9","stable_key":"f812c44f-d0fd-5f01-ba2c-748c0794fcfb:coumarin-methoxsalen-inactivation-event","event_type":"biochemical_relationship","label":"Methoxsalen can disable this enzyme during metabolism.","description":"Methoxsalen produced mechanism-based CYP2A6 inhibition, with reported inactivation rate 0.5/min.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3221abe0-7cbd-5889-a2bf-7ba8e56567a2","slug":"methoxsalen","display_name":"Methoxsalen / 8-methoxypsoralen","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"44b7b150-3615-5d52-9db8-beb212fc31eb","slug":"cyp2a6","display_name":"Human cytochrome P450 2A6 / CYP2A6","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/coumarin-research/9143352.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09\", \"start_char\": 0, \"end_char\": 2723, \"text_sha256\": \"dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human microsomal and recombinant CYP2A6 inhibitor screen","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Coumarin 0.5–50 micromolar; 47 inhibitor/substrate probes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"In vitro inhibition thresholds are not demonstrated clinical interactions at food exposure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Coumarin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"coumarin","display_name":"Coumarin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Methoxsalen can disable this enzyme during metabolism.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[coumarin-p9143352] Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. (1997). https://pubmed.ncbi.nlm.nih.gov/9143352/ DOI: 10.1006/abbi.1997.9964","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Liver enzyme preparations","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"e0b84516-e6dc-5157-856f-6ce8c7173b2c","evidence_kind":"source_excerpt","locator":"Lines 553-564","start_line":553,"end_line":564,"excerpt":"### coumarin-methoxsalen-inactivation\nMethoxsalen produced mechanism-based CYP2A6 inhibition, with reported inactivation rate 0.5/min.\nCondition category: normal\nnutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Methoxsalen can disable this enzyme during metabolism.\norganism: Human\ntissue_or_cell_type: Liver enzyme preparations\nexperimental_model: Human microsomal and recombinant CYP2A6 inhibitor screen\nlimitations: In vitro inhibition thresholds are not demonstrated clinical interactions at food exposure.\nexposure: Coumarin 0.5–50 micromolar; 47 inhibitor/substrate probes\nevidence_span: {\"source_cache\": \"artifacts/coumarin-research/9143352.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09\", \"start_char\": 0, \"end_char\": 2723, \"text_sha256\": \"dca3f4253c2977d47070bb95696634ee2e06fa9a28a3d76ac9790ce695ed6f09\"}\n[coumarin-p9143352] Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. 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