{"id":"b140347b-0431-5c17-b3e8-838df49101a1","stable_key":"3d41d18a-e13a-59a0-a081-55bfcdd43e55:ceylon-predicted-letrozole","predicate":"is_predicted_to_increase","statement":"The rat-scaled static model predicted a 4.92-fold letrozole AUC with the modeled cinnamaldehyde exposure.","claim_class":"hypothesis_link","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"eafa0ff4-73fb-5966-a8c7-01c111549da2","mechanism_event_label":"This was a forecast from enzyme data and assumptions, not a result in people.","subject":{"id":"2dc093c6-9373-5b24-a17b-a6b21b5a0432","slug":"trans-cinnamaldehyde","display_name":"trans-Cinnamaldehyde / cinnamal","entity_type_key":"small_molecule"},"object":{"id":"755aa632-c0f8-5e12-ac47-2c55024bc846","slug":"predicted-letrozole-auc","display_name":"Model-predicted letrozole plasma exposure AUC","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"eafa0ff4-73fb-5966-a8c7-01c111549da2","stable_key":"3d41d18a-e13a-59a0-a081-55bfcdd43e55:ceylon-predicted-letrozole-event","event_type":"biochemical_relationship","label":"This was a forecast from enzyme data and assumptions, not a result in people.","description":"The rat-scaled static model predicted a 4.92-fold letrozole AUC with the modeled cinnamaldehyde exposure.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"44b7b150-3615-5d52-9db8-beb212fc31eb","slug":"cyp2a6","display_name":"Human cytochrome P450 2A6 / CYP2A6","entity_type_key":"protein"},"role":"modeled_clearance_enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"aa35f145-142d-5f78-950f-3c9ef2753656","slug":"letrozole","display_name":"Letrozole","entity_type_key":"small_molecule"},"role":"modeled_substrate","stoichiometry":null,"state_label":"","sequence_order":1,"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":2,"notes":""},{"entity":{"id":"755aa632-c0f8-5e12-ac47-2c55024bc846","slug":"predicted-letrozole-auc","display_name":"Model-predicted letrozole plasma exposure AUC","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/ceylon-research/32788161.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"431169f83241cb83b84dd81d84eb1db225735677cabf33f09af8b1e22dfe64f4\", \"start_char\": 0, \"end_char\": 2507, \"text_sha256\": \"431169f83241cb83b84dd81d84eb1db225735677cabf33f09af8b1e22dfe64f4\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"CYP2A6 mass spectrometry, time-dependent inhibition and numerical modeling","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Cinnamaldehyde and separately 2-methoxycinnamaldehyde; model exposure approximately 275 mg cinnamaldehyde","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Rat-scaled predicted human AUC is not observed AUC. Heme loss was specifically reported for the methoxy analogue; apoprotein adduction is a different endpoint from inhibition.","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 CYP2A6; rat-scaled modeling parameters","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This was a forecast from enzyme data and assumptions, not a result in people.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ceylon-p32788161] Mechanisms of Herb-Drug Interactions Involving Cinnamon and CYP2A6: Focus on Time-Dependent Inhibition by Cinnamaldehyde and 2-Methoxycinnamaldehyde. (2020). https://pubmed.ncbi.nlm.nih.gov/32788161/ DOI: 10.1124/dmd.120.000087","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Enzyme apoprotein/heme; simulated drug exposure","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"c5dd21e4-c510-58dd-ade6-3272cfcae414","evidence_kind":"source_excerpt","locator":"Lines 805-816","start_line":805,"end_line":816,"excerpt":"### ceylon-predicted-letrozole\nThe rat-scaled static model predicted a 4.92-fold letrozole AUC with the modeled cinnamaldehyde exposure.\nCondition category: normal\nnutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This was a forecast from enzyme data and assumptions, not a result in people.\norganism: Human CYP2A6; rat-scaled modeling parameters\ntissue_or_cell_type: Enzyme apoprotein/heme; simulated drug exposure\nexperimental_model: CYP2A6 mass spectrometry, time-dependent inhibition and numerical modeling\nlimitations: Rat-scaled predicted human AUC is not observed AUC. Heme loss was specifically reported for the methoxy analogue; apoprotein adduction is a different endpoint from inhibition.\nexposure: Cinnamaldehyde and separately 2-methoxycinnamaldehyde; model exposure approximately 275 mg cinnamaldehyde\nevidence_span: {\"source_cache\": \"artifacts/ceylon-research/32788161.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"431169f83241cb83b84dd81d84eb1db225735677cabf33f09af8b1e22dfe64f4\", \"start_char\": 0, \"end_char\": 2507, \"text_sha256\": \"431169f83241cb83b84dd81d84eb1db225735677cabf33f09af8b1e22dfe64f4\"}\n[ceylon-p32788161] Mechanisms of Herb-Drug Interactions Involving Cinnamon and CYP2A6: Focus on Time-Dependent Inhibition by Cinnamaldehyde and 2-Methoxycinnamaldehyde. (2020). https://pubmed.ncbi.nlm.nih.gov/32788161/ DOI: 10.1124/dmd.120.000087","model_system":"CYP2A6 mass spectrometry, time-dependent inhibition and numerical modeling","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ceylon-p32788161] Mechanisms of Herb-Drug Interactions Involving Cinnamon and CYP2A6: Focus on Time-Dependent Inhibition by Cinnamaldehyde and 2-Methoxycinnamaldehyde. (2020). https://pubmed.ncbi.nlm.nih.gov/32788161/ DOI: 10.1124/dmd.120.000087","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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