{"id":"dd7bdee1-2c5d-59ea-b611-dc1a1613824e","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-clozapine-1a2","predicate":"demethylates","statement":"CYP1A2 contributed to clozapine demethylation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"f6b47350-142a-54c1-810b-b02dba5ab400","mechanism_event_label":"Clozapine shares an enzyme that DIM can induce in laboratory systems; its response to DIM was not measured.","subject":{"id":"9b15c13c-a369-5d10-a76a-525e8b19221d","slug":"cyp1a2","display_name":"Human cytochrome P450 1A2","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":"f6b47350-142a-54c1-810b-b02dba5ab400","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-clozapine-1a2-event","event_type":"biochemical_relationship","label":"Clozapine shares an enzyme that DIM can induce in laboratory systems; its response to DIM was not measured.","description":"CYP1A2 contributed to clozapine demethylation.","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":"9b15c13c-a369-5d10-a76a-525e8b19221d","slug":"cyp1a2","display_name":"Human cytochrome P450 1A2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"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":2,"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 shares an enzyme that DIM can induce in laboratory systems; its response to DIM was not measured.","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":"14f14884-eda4-55ff-ac75-e5a555fa8398","evidence_kind":"source_excerpt","locator":"Lines 662-673","start_line":662,"end_line":673,"excerpt":"### dim-clozapine-1a2\nCYP1A2 contributed to clozapine demethylation.\nCondition category: normal\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Clozapine shares an enzyme that DIM can induce in laboratory systems; its response to DIM was not measured.\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. Study references: [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","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"b6d70682-97f9-5893-a03c-f9f88836033c","stable_key":"import-182336c6-ed36-5ec6-8a09-25c31096262e","title":"Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"31e14060de904976d2f5d439f2bc9c8a99a72d34626c562c78429025e050d404","revision_id":"611094c1-a9cf-5b9b-b255-ac70b571696a","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}