{"id":"a45599c0-850e-53d4-a19e-d218710c3a6c","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-propranolol-1a2","predicate":"supports_n_desisopropylation_of","statement":"CYP1A2 contributed prominently to propranolol N-desisopropylation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"07ccda22-6f44-547a-8e7f-381a33b89182","mechanism_event_label":"This is one route through a drug with several clearance mechanisms.","subject":{"id":"9b15c13c-a369-5d10-a76a-525e8b19221d","slug":"cyp1a2","display_name":"Human cytochrome P450 1A2","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":"07ccda22-6f44-547a-8e7f-381a33b89182","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-propranolol-1a2-event","event_type":"biochemical_relationship","label":"This is one route through a drug with several clearance mechanisms.","description":"CYP1A2 contributed prominently to propranolol N-desisopropylation.","status":"provisional","compartment":null,"participants":[{"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":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":"This is one route through a drug with several clearance mechanisms.","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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