{"id":"7fc2b5c2-0bf1-5b5a-9413-26d9876d2f09","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-propranolol-2d6","predicate":"supports_4_hydroxylation_of","statement":"CYP2D6 was a major catalyst of propranolol ring 4-hydroxylation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"f5c2ee6b-a90b-5de5-a50e-8c608e9fdb3b","mechanism_event_label":"A separate enzyme supports a different transformation of the same drug.","subject":{"id":"10f7a103-d63d-5bf4-8384-c5e1308ce126","slug":"cyp2d6","display_name":"Human cytochrome P450 2D6","entity_type_key":"protein"},"object":{"id":"01b9c67d-436d-523a-8f78-53cad2b521ce","slug":"propranolol","display_name":"Propranolol","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"f5c2ee6b-a90b-5de5-a50e-8c608e9fdb3b","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-propranolol-2d6-event","event_type":"biochemical_relationship","label":"A separate enzyme supports a different transformation of the same drug.","description":"CYP2D6 was a major catalyst of propranolol ring 4-hydroxylation.","status":"provisional","compartment":null,"participants":[{"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":0,"notes":""},{"entity":{"id":"01b9c67d-436d-523a-8f78-53cad2b521ce","slug":"propranolol","display_name":"Propranolol","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dim-research/7640150.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"368198090ed645914a14e9d365b48030bcfd8a67e4d5bc4f9f6d1476e8340247\", \"start_char\": 0, \"end_char\": 2428, \"text_sha256\": \"368198090ed645914a14e9d365b48030bcfd8a67e4d5bc4f9f6d1476e8340247\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human microsomes and recombinant enzyme phenotyping","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"N-desisopropylation versus ring hydroxylation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Route- and enantiomer-specific biochemistry; total propranolol exposure cannot be predicted from one route.","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 isoforms","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A separate enzyme supports a different transformation of the same drug.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p7640150] Identification of human CYP isoforms involved in the metabolism of propranolol enantiomers--N-desisopropylation is mediated mainly by CYP1A2. 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(1995). https://pubmed.ncbi.nlm.nih.gov/7640150/ DOI: 10.1111/j.1365-2125.1995.tb04472.x","model_system":"Human microsomes and recombinant enzyme phenotyping","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [dim-p7640150] Identification of human CYP isoforms involved in the metabolism of propranolol enantiomers--N-desisopropylation is mediated mainly by CYP1A2. 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