{"id":"f328e03b-dc94-5b84-9498-f376d9db28d0","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-tamoxifen-endoxifen","predicate":"forms_endoxifen_from","statement":"Conversion of N-desmethyltamoxifen to endoxifen was catalyzed by CYP2D6 in the tested system.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e596f958-55a3-5b6b-a6f0-ddaae9650cbd","mechanism_event_label":"The key activation step cannot be replaced by the statement that CYP1A2 is induced.","subject":{"id":"10f7a103-d63d-5bf4-8384-c5e1308ce126","slug":"cyp2d6","display_name":"Human cytochrome P450 2D6","entity_type_key":"protein"},"object":{"id":"eb1d312a-027c-5f96-8995-d115854b9b07","slug":"n-desmethyltamoxifen","display_name":"N-Desmethyltamoxifen","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"e596f958-55a3-5b6b-a6f0-ddaae9650cbd","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-tamoxifen-endoxifen-event","event_type":"biochemical_relationship","label":"The key activation step cannot be replaced by the statement that CYP1A2 is induced.","description":"Conversion of N-desmethyltamoxifen to endoxifen was catalyzed by CYP2D6 in the tested system.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"273b0b15-4e38-5918-9958-29dac49f6345","slug":"endoxifen","display_name":"Endoxifen / 4-hydroxy-N-desmethyltamoxifen","entity_type_key":"small_molecule"},"role":"active_product","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"10f7a103-d63d-5bf4-8384-c5e1308ce126","slug":"cyp2d6","display_name":"Human cytochrome P450 2D6","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"eb1d312a-027c-5f96-8995-d115854b9b07","slug":"n-desmethyltamoxifen","display_name":"N-Desmethyltamoxifen","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/15159443.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081\", \"start_char\": 0, \"end_char\": 1544, \"text_sha256\": \"0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Kinetic, inhibition and recombinant-enzyme pathway mapping","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Therapeutically relevant substrate concentrations","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Biochemical pathway identity; does not attribute the observed DIM interaction to any single CYP or prove clinical cancer outcomes.","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 liver microsomes and expressed CYPs","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The key activation step cannot be replaced by the statement that CYP1A2 is induced.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p15159443] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. 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