{"id":"cc52973e-df67-5ee6-a65e-e7b3f552c874","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-ramelteon-cyp1a2","predicate":"metabolizes","statement":"CYP1A2 catalyzed ramelteon metabolism in the tested microsomal/recombinant system.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"bec03d81-4ad0-51d5-bbc6-c66002db8d5d","mechanism_event_label":"Ramelteon has several metabolic routes; none here measures a DIM interaction.","subject":{"id":"9b15c13c-a369-5d10-a76a-525e8b19221d","slug":"cyp1a2","display_name":"Human cytochrome P450 1A2","entity_type_key":"protein"},"object":{"id":"5823c263-2861-59e3-8caf-055263c3b932","slug":"ramelteon","display_name":"Ramelteon","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"bec03d81-4ad0-51d5-bbc6-c66002db8d5d","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-ramelteon-cyp1a2-event","event_type":"biochemical_relationship","label":"Ramelteon has several metabolic routes; none here measures a DIM interaction.","description":"CYP1A2 catalyzed ramelteon metabolism in the tested microsomal/recombinant system.","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":"5823c263-2861-59e3-8caf-055263c3b932","slug":"ramelteon","display_name":"Ramelteon","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/20478852.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e\", \"start_char\": 0, \"end_char\": 1696, \"text_sha256\": \"0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Microsomal metabolism and drug-interaction prediction","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"CYP1A2, CYP2C19 and CYP3A4 assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"In-vitro estimated shares vary by pathway and model. Fluvoxamine inhibits multiple routes; its large interaction cannot be inverted into a DIM prediction.","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 and intestinal microsomes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Ramelteon has several metabolic routes; none here measures a DIM interaction.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p20478852] Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. (2010). https://pubmed.ncbi.nlm.nih.gov/20478852/ DOI: 10.1124/dmd.110.034009","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Ramelteon metabolism","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b30ef2f5-a153-5965-8851-eda49188b8c2","evidence_kind":"source_excerpt","locator":"Lines 870-881","start_line":870,"end_line":881,"excerpt":"### dim-ramelteon-cyp1a2\nCYP1A2 catalyzed ramelteon metabolism in the tested microsomal/recombinant system.\nCondition category: normal\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Ramelteon has several metabolic routes; none here measures a DIM interaction.\norganism: Human liver and intestinal microsomes\ntissue_or_cell_type: Ramelteon metabolism\nexperimental_model: Microsomal metabolism and drug-interaction prediction\nlimitations: In-vitro estimated shares vary by pathway and model. Fluvoxamine inhibits multiple routes; its large interaction cannot be inverted into a DIM prediction.\nexposure: CYP1A2, CYP2C19 and CYP3A4 assays\nevidence_span: {\"source_cache\": \"artifacts/dim-research/20478852.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e\", \"start_char\": 0, \"end_char\": 1696, \"text_sha256\": \"0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e\"}\n[dim-p20478852] Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. (2010). https://pubmed.ncbi.nlm.nih.gov/20478852/ DOI: 10.1124/dmd.110.034009","model_system":"Microsomal metabolism and drug-interaction prediction","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [dim-p20478852] Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. (2010). https://pubmed.ncbi.nlm.nih.gov/20478852/ DOI: 10.1124/dmd.110.034009","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}