{"id":"ff88753a-87a5-58d6-a918-a9c0e5d4a707","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-cyp1a2-direct-inhibition","predicate":"directly_inhibits_in_assay","statement":"DIM directly inhibited CYP1A2 catalytic activity in the tested enzyme assay.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"40f8d6f3-daf9-5064-a5bc-8ff3c05dac5f","mechanism_event_label":"Direct enzyme inhibition can oppose a slower increase in enzyme production.","subject":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"object":{"id":"9b15c13c-a369-5d10-a76a-525e8b19221d","slug":"cyp1a2","display_name":"Human cytochrome P450 1A2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"40f8d6f3-daf9-5064-a5bc-8ff3c05dac5f","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-cyp1a2-direct-inhibition-event","event_type":"biochemical_relationship","label":"Direct enzyme inhibition can oppose a slower increase in enzyme production.","description":"DIM directly inhibited CYP1A2 catalytic activity in the tested enzyme assay.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9b15c13c-a369-5d10-a76a-525e8b19221d","slug":"cyp1a2","display_name":"Human cytochrome P450 1A2","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dim-research/19770484.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba\", \"start_char\": 0, \"end_char\": 1446, \"text_sha256\": \"b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Pretreatment versus cotreatment, adduct and recombinant-enzyme assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"DIM pretreatment for 48 hours; direct catalytic assays separately","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Induction over time and direct inhibition are distinct mechanisms. Aflatoxin assay effects do not establish human cancer incidence or net disposition of unrelated drugs.","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":"Primary human hepatocytes and human enzyme preparations","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Direct enzyme inhibition can oppose a slower increase in enzyme production.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p19770484] Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols. (2009). https://pubmed.ncbi.nlm.nih.gov/19770484/ DOI: 10.1093/toxsci/kfp206","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Aflatoxin metabolism and CYP catalytic activity","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"315f212f-dcac-5b47-b271-bf2ba36c564b","evidence_kind":"source_excerpt","locator":"Lines 441-452","start_line":441,"end_line":452,"excerpt":"### dim-cyp1a2-direct-inhibition\nDIM directly inhibited CYP1A2 catalytic activity in the tested enzyme assay.\nCondition category: normal\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Direct enzyme inhibition can oppose a slower increase in enzyme production.\norganism: Primary human hepatocytes and human enzyme preparations\ntissue_or_cell_type: Aflatoxin metabolism and CYP catalytic activity\nexperimental_model: Pretreatment versus cotreatment, adduct and recombinant-enzyme assays\nlimitations: Induction over time and direct inhibition are distinct mechanisms. Aflatoxin assay effects do not establish human cancer incidence or net disposition of unrelated drugs.\nexposure: DIM pretreatment for 48 hours; direct catalytic assays separately\nevidence_span: {\"source_cache\": \"artifacts/dim-research/19770484.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba\", \"start_char\": 0, \"end_char\": 1446, \"text_sha256\": \"b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba\"}\n[dim-p19770484] Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols. 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