{"id":"5a2dad03-ea77-5618-974d-227075531bab","stable_key":"f812c44f-d0fd-5f01-ba2c-748c0794fcfb:coumarin-tranylcypromine-inhibition","predicate":"competitively_inhibits","statement":"Tranylcypromine competitively inhibited coumarin 7-hydroxylation, with Ki 0.04 micromolar.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"88f51376-e921-52d1-9c32-7b787a501723","mechanism_event_label":"A medicine inhibited the coumarin-processing reaction in vitro.","subject":{"id":"3a1d00eb-0ac5-575f-8264-fc28392b6f99","slug":"tranylcypromine","display_name":"Tranylcypromine","entity_type_key":"small_molecule"},"object":{"id":"8a5084db-2b31-59a9-8afc-3ad0980d8f5d","slug":"coumarin-7-hydroxylation","display_name":"Coumarin 7-hydroxylation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"88f51376-e921-52d1-9c32-7b787a501723","stable_key":"f812c44f-d0fd-5f01-ba2c-748c0794fcfb:coumarin-tranylcypromine-inhibition-event","event_type":"biochemical_relationship","label":"A medicine inhibited the coumarin-processing reaction in vitro.","description":"Tranylcypromine competitively inhibited coumarin 7-hydroxylation, with Ki 0.04 micromolar.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3a1d00eb-0ac5-575f-8264-fc28392b6f99","slug":"tranylcypromine","display_name":"Tranylcypromine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8a5084db-2b31-59a9-8afc-3ad0980d8f5d","slug":"coumarin-7-hydroxylation","display_name":"Coumarin 7-hydroxylation","entity_type_key":"cellular_process"},"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":"A medicine inhibited the coumarin-processing reaction in vitro.","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":"42567714-8cb3-5385-8784-a57afe46a642","evidence_kind":"source_excerpt","locator":"Lines 566-577","start_line":566,"end_line":577,"excerpt":"### coumarin-tranylcypromine-inhibition\nTranylcypromine competitively inhibited coumarin 7-hydroxylation, with Ki 0.04 micromolar.\nCondition category: normal\nnutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A medicine inhibited the coumarin-processing reaction in vitro.\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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