{"id":"51d5d32f-4511-5623-b5e3-3af4e5d09620","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-clozapine-3a4","predicate":"oxidizes","statement":"CYP3A4 contributed to clozapine demethylation and N-oxidation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"f8eee7e6-d611-577d-8e8c-b0eca1642087","mechanism_event_label":"Clozapine has more than one relevant route.","subject":{"id":"54e95ff1-4ffa-5e6f-a4cb-b47e5d2a5bda","slug":"cyp3a4","display_name":"Human cytochrome P450 3A4","entity_type_key":"protein"},"object":{"id":"2131891d-599e-5f0d-99f2-641cbbae52a7","slug":"clozapine","display_name":"Clozapine","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"f8eee7e6-d611-577d-8e8c-b0eca1642087","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-clozapine-3a4-event","event_type":"biochemical_relationship","label":"Clozapine has more than one relevant route.","description":"CYP3A4 contributed to clozapine demethylation and N-oxidation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9efe4e82-58af-5ec5-90d4-ba81b0a44d84","slug":"desmethylclozapine","display_name":"Desmethylclozapine / norclozapine","entity_type_key":"small_molecule"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1d22c1e0-3707-5528-b9d5-b7aba83c8653","slug":"clozapine-n-oxide","display_name":"Clozapine N-oxide","entity_type_key":"small_molecule"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"54e95ff1-4ffa-5e6f-a4cb-b47e5d2a5bda","slug":"cyp3a4","display_name":"Human cytochrome P450 3A4","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"2131891d-599e-5f0d-99f2-641cbbae52a7","slug":"clozapine","display_name":"Clozapine","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dim-research/9384460.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"eb481193bb0d7564d728a25a9ddd63678e8234e628edca3f13ece910770279b6\", \"start_char\": 0, \"end_char\": 1794, \"text_sha256\": \"eb481193bb0d7564d728a25a9ddd63678e8234e628edca3f13ece910770279b6\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant enzymes, antibodies and human liver microsomes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Enzyme-specific inhibition and metabolite formation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Identifies metabolic routes, not a trial of DIM with clozapine. Do not infer a dose change or magnitude of interaction.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human CYP enzymes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Clozapine has more than one relevant route.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p9384460] The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. (1997). https://pubmed.ncbi.nlm.nih.gov/9384460/ DOI: 10.1046/j.1365-2125.1997.t01-1-00605.x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Clozapine oxidation","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"6b96fbc3-7116-5949-91a9-415566c8175e","evidence_kind":"source_excerpt","locator":"Lines 675-686","start_line":675,"end_line":686,"excerpt":"### dim-clozapine-3a4\nCYP3A4 contributed to clozapine demethylation and N-oxidation.\nCondition category: normal\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Clozapine has more than one relevant route.\norganism: Human CYP enzymes\ntissue_or_cell_type: Clozapine oxidation\nexperimental_model: Recombinant enzymes, antibodies and human liver microsomes\nlimitations: Identifies metabolic routes, not a trial of DIM with clozapine. Do not infer a dose change or magnitude of interaction.\nexposure: Enzyme-specific inhibition and metabolite formation\nevidence_span: {\"source_cache\": \"artifacts/dim-research/9384460.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"eb481193bb0d7564d728a25a9ddd63678e8234e628edca3f13ece910770279b6\", \"start_char\": 0, \"end_char\": 1794, \"text_sha256\": \"eb481193bb0d7564d728a25a9ddd63678e8234e628edca3f13ece910770279b6\"}\n[dim-p9384460] The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. (1997). https://pubmed.ncbi.nlm.nih.gov/9384460/ DOI: 10.1046/j.1365-2125.1997.t01-1-00605.x","model_system":"Recombinant enzymes, antibodies and human liver microsomes","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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