{"id":"ca57a2b2-c439-551f-8e4d-ffc4319c7764","stable_key":"3d41d18a-e13a-59a0-a081-55bfcdd43e55:ceylon-cyp2a6","predicate":"inhibits","statement":"Cinnamaldehyde inhibited recombinant human CYP2A6, with reported IC50 6.1 micromolar; inhibition increased with time and required NADPH.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"556930a5-f997-5e0c-8f74-5ee323b2e712","mechanism_event_label":"The chemical interfered with a drug-metabolizing enzyme when its catalytic system was operating.","subject":{"id":"2dc093c6-9373-5b24-a17b-a6b21b5a0432","slug":"trans-cinnamaldehyde","display_name":"trans-Cinnamaldehyde / cinnamal","entity_type_key":"small_molecule"},"object":{"id":"44b7b150-3615-5d52-9db8-beb212fc31eb","slug":"cyp2a6","display_name":"Human cytochrome P450 2A6 / CYP2A6","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"556930a5-f997-5e0c-8f74-5ee323b2e712","stable_key":"3d41d18a-e13a-59a0-a081-55bfcdd43e55:ceylon-cyp2a6-event","event_type":"biochemical_relationship","label":"The chemical interfered with a drug-metabolizing enzyme when its catalytic system was operating.","description":"Cinnamaldehyde inhibited recombinant human CYP2A6, with reported IC50 6.1 micromolar; inhibition increased with time and required NADPH.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"4aba2a5e-8d06-5304-bb01-c0402b225a94","slug":"nadph","display_name":"NADPH","entity_type_key":"small_molecule"},"role":"required_reducing_cofactor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2dc093c6-9373-5b24-a17b-a6b21b5a0432","slug":"trans-cinnamaldehyde","display_name":"trans-Cinnamaldehyde / cinnamal","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"44b7b150-3615-5d52-9db8-beb212fc31eb","slug":"cyp2a6","display_name":"Human cytochrome P450 2A6 / CYP2A6","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/ceylon-research/26851241.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2\", \"start_char\": 0, \"end_char\": 1591, \"text_sha256\": \"c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant human CYP assays and mechanistic static modeling","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Cinnamaldehyde, NADPH and glutathione; modeled inhibitor concentrations 0.1 and 1 micromolar","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Enzyme inhibition and model predictions are not measured clinical drug interactions. NADPH omission is not dietary niacin deficiency.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"ceylon","display_name":"Ceylon cinnamon / Cinnamomum verum bark preparations","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Human enzyme preparations; computational model","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The chemical interfered with a drug-metabolizing enzyme when its catalytic system was operating.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ceylon-p26851241] Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole. (2016). https://pubmed.ncbi.nlm.nih.gov/26851241/ DOI: 10.1124/dmd.115.067942","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"CYP2A6 reaction system","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"d06d5c88-167a-5983-964b-06c57c146059","evidence_kind":"source_excerpt","locator":"Lines 727-738","start_line":727,"end_line":738,"excerpt":"### ceylon-cyp2a6\nCinnamaldehyde inhibited recombinant human CYP2A6, with reported IC50 6.1 micromolar; inhibition increased with time and required NADPH.\nCondition category: normal\nnutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The chemical interfered with a drug-metabolizing enzyme when its catalytic system was operating.\norganism: Human enzyme preparations; computational model\ntissue_or_cell_type: CYP2A6 reaction system\nexperimental_model: Recombinant human CYP assays and mechanistic static modeling\nlimitations: Enzyme inhibition and model predictions are not measured clinical drug interactions. NADPH omission is not dietary niacin deficiency.\nexposure: Cinnamaldehyde, NADPH and glutathione; modeled inhibitor concentrations 0.1 and 1 micromolar\nevidence_span: {\"source_cache\": \"artifacts/ceylon-research/26851241.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2\", \"start_char\": 0, \"end_char\": 1591, \"text_sha256\": \"c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2\"}\n[ceylon-p26851241] Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole. (2016). https://pubmed.ncbi.nlm.nih.gov/26851241/ DOI: 10.1124/dmd.115.067942","model_system":"Recombinant human CYP assays and mechanistic static modeling","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ceylon-p26851241] Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole. (2016). https://pubmed.ncbi.nlm.nih.gov/26851241/ DOI: 10.1124/dmd.115.067942","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"3aed3c5b-8016-5e37-ad6f-9019d34d19eb","stable_key":"import-3d41d18a-e13a-59a0-a081-55bfcdd43e55","title":"Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. 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