{"id":"56c5ae49-907a-5934-91ac-88fb67325471","stable_key":"7de430a5-1a36-5231-b931-35cc01d8f3bf:apap-unlikely-in-any-species","predicate":"limits","statement":"Although COX-3 might have cyclooxygenase activity in canines and that activity might be inhibited by acetaminophen, its low expression level and the kinetics indicate unlikely clinical relevance, and in rodents and humans COX-3 encodes proteins with completely different amino acid sequences than cyclooxygenase-1 or -2 and without cyclooxygenase activity, so it is improbable that it plays a role in prostaglandin-mediated fever and pain in these species.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"308efe57-2f80-552c-8d3e-4b38cefc4e06","mechanism_event_label":"Even in the dog the amounts are too small to matter, and in people the protein is not an enzyme.","subject":{"id":"a4c9b287-5373-57d2-b126-f1290d79343a","slug":"cox-3","display_name":"COX-3 / COX-1b, a cyclooxygenase-1 transcript retaining intron 1","entity_type_key":"protein"},"object":{"id":"f0247ef6-fe4d-5a7d-9621-434407dc3806","slug":"antipyresis","display_name":"Reduction of a raised body temperature","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"308efe57-2f80-552c-8d3e-4b38cefc4e06","stable_key":"7de430a5-1a36-5231-b931-35cc01d8f3bf:apap-unlikely-in-any-species-event","event_type":"observed_intervention","label":"Even in the dog the amounts are too small to matter, and in people the protein is not an enzyme.","description":"Although COX-3 might have cyclooxygenase activity in canines and that activity might be inhibited by acetaminophen, its low expression level and the kinetics indicate unlikely clinical relevance, and in rodents and humans COX-3 encodes proteins with completely different amino acid sequences than cyclooxygenase-1 or -2 and without cyclooxygenase activity, so it is improbable that it plays a role in prostaglandin-mediated fever and pain in these species.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a901be21-7915-543c-ac67-c39ef72b0d03","slug":"acetaminophen","display_name":"Paracetamol","entity_type_key":"drug"},"role":"drug_in_question","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6284d26c-01e2-5e12-b192-ee391dd107e2","slug":"ptgs1","display_name":"Cyclooxygenase-1 (PTGS1)","entity_type_key":"protein"},"role":"related_isoform","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a4c9b287-5373-57d2-b126-f1290d79343a","slug":"cox-3","display_name":"COX-3 / COX-1b, a cyclooxygenase-1 transcript retaining intron 1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"f0247ef6-fe4d-5a7d-9621-434407dc3806","slug":"antipyresis","display_name":"Reduction of a raised body temperature","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/paracetamol-research/15879007.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"857ae81119eac4c47a63027afa15fde1b0099c377c0d444e13da087ea71dec86\", \"start_char\": 0, \"end_char\": 807, \"text_sha256\": \"857ae81119eac4c47a63027afa15fde1b0099c377c0d444e13da087ea71dec86\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Critical review of the COX-3 literature","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Evaluation of the expression levels, kinetics and species differences of the proposed isoform","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A review rather than new data. It states the species-specific reason the proposal fails and the reason it would not matter even where the protein is active.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404.","comparator":null,"unit":null,"notes":"","entity":{"slug":"acetaminophen","display_name":"Paracetamol","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Dog, rodent and human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Even in the dog the amounts are too small to matter, and in people the protein is not an enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[apap-p15879007] Acetaminophen and the cyclooxygenase-3 puzzle: sorting out facts, fictions, and uncertainties. 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It states the species-specific reason the proposal fails and the reason it would not matter even where the protein is active.\nexposure: Evaluation of the expression levels, kinetics and species differences of the proposed isoform\nevidence_span: {\"source_cache\": \"artifacts/paracetamol-research/15879007.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"857ae81119eac4c47a63027afa15fde1b0099c377c0d444e13da087ea71dec86\", \"start_char\": 0, \"end_char\": 807, \"text_sha256\": \"857ae81119eac4c47a63027afa15fde1b0099c377c0d444e13da087ea71dec86\"}\n[apap-p15879007] Acetaminophen and the cyclooxygenase-3 puzzle: sorting out facts, fictions, and uncertainties. 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