{"id":"480ca82d-a238-5585-83c0-730757c21bd6","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-olanzapine-ugt","predicate":"forms_from_olanzapine","statement":"UGT1A4 played a major role in olanzapine 10-N-glucuronide formation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"2a30f8a5-b493-5e18-adb1-fed631fed00c","mechanism_event_label":"This independently identified route also contributes to olanzapine handling.","subject":{"id":"3d90e9e4-9b25-5238-889b-53f0d21fa1a1","slug":"ugt1a4","display_name":"Human UDP-glucuronosyltransferase 1A4","entity_type_key":"protein"},"object":{"id":"0cad521f-7087-5805-9928-55f8f71315ee","slug":"olanzapine-10-n-glucuronide","display_name":"Olanzapine 10-N-glucuronide","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"2a30f8a5-b493-5e18-adb1-fed631fed00c","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-olanzapine-ugt-event","event_type":"biochemical_relationship","label":"This independently identified route also contributes to olanzapine handling.","description":"UGT1A4 played a major role in olanzapine 10-N-glucuronide formation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e83902e5-cd44-5de2-b790-abf19033d265","slug":"olanzapine","display_name":"Olanzapine","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3d90e9e4-9b25-5238-889b-53f0d21fa1a1","slug":"ugt1a4","display_name":"Human UDP-glucuronosyltransferase 1A4","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"0cad521f-7087-5805-9928-55f8f71315ee","slug":"olanzapine-10-n-glucuronide","display_name":"Olanzapine 10-N-glucuronide","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/26329789.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543\", \"start_char\": 0, \"end_char\": 1657, \"text_sha256\": \"1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human liver microsomes and recombinant enzyme phenotyping","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Metabolite-specific assays including albumin effects","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"In-vitro relative contributions; no DIM coadministration. Multiple routes limit prediction from CYP1A2 alone.","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, FMO and UGT enzymes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This independently identified route also contributes to olanzapine handling.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p26329789] In Vitro Characterization of the Human Liver Microsomal Kinetics and Reaction Phenotyping of Olanzapine Metabolism. (2015). https://pubmed.ncbi.nlm.nih.gov/26329789/ DOI: 10.1124/dmd.115.064790","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Olanzapine oxidation and conjugation","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"eb0c9b25-460f-5d00-a8cc-3f0269794173","evidence_kind":"source_excerpt","locator":"Lines 714-725","start_line":714,"end_line":725,"excerpt":"### dim-olanzapine-ugt\nUGT1A4 played a major role in olanzapine 10-N-glucuronide formation.\nCondition category: normal\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This independently identified route also contributes to olanzapine handling.\norganism: Human CYP, FMO and UGT enzymes\ntissue_or_cell_type: Olanzapine oxidation and conjugation\nexperimental_model: Human liver microsomes and recombinant enzyme phenotyping\nlimitations: In-vitro relative contributions; no DIM coadministration. Multiple routes limit prediction from CYP1A2 alone.\nexposure: Metabolite-specific assays including albumin effects\nevidence_span: {\"source_cache\": \"artifacts/dim-research/26329789.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543\", \"start_char\": 0, \"end_char\": 1657, \"text_sha256\": \"1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543\"}\n[dim-p26329789] In Vitro Characterization of the Human Liver Microsomal Kinetics and Reaction Phenotyping of Olanzapine Metabolism. (2015). https://pubmed.ncbi.nlm.nih.gov/26329789/ DOI: 10.1124/dmd.115.064790","model_system":"Human liver microsomes and recombinant enzyme phenotyping","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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