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Cyclooxygenase-3 (COX-3) (COX-3)
- Target
- COX-3
- Molecular classification
- Enzyme, Oxidoreductase, Heme peroxidase family
01
Overview
Cyclooxygenase-3 (COX-3) is a splice variant of the cyclooxygenase-1 (COX-1, PTGS1) gene, retaining intron 1, and is most abundantly expressed in the brain. Unlike COX-2, which is inducible and peripherally expressed, COX-3 is proposed to contribute to the central mechanisms of pain and fever. COX-3 is selectively inhibited by acetaminophen and related drugs, explaining the antipyretic and analgesic effects of these agents with minimal anti-inflammatory action. The physiological and pathological significance of COX-3 is still not fully characterized, and it is less studied than COX-1 and COX-2.
- Other names
- Cyclooxygenase-3COX-3PGHS-3central COXCNS COXcyclooxygenase-1 splice variantCOXProstaglandin G/H synthaseCyclooxygenase-1 variant
02
Mechanism of action
Inhibition of cyclooxygenase activity, reducing prostaglandin synthesis in CNS and thereby modulating pain and fever
03
Biological functions
Prostaglandin synthesisLipid metabolismInflammatory response
04
Disease associations
PainFeverInflammationNeurological disorders (implicated in CNS inflammation)
05
Safety considerations
Off-target effects due to lack of selectivity among COX isoformsPotential for liver toxicity (due to acetaminophen metabolism, not COX-3 per se)Unclear physiological role and tissue distribution, complicating targeted therapy
06
Interacting drugs
Acetaminophen (paracetamol)
2 more in the full profile.
07
Biomarkers
No established clinical biomarkers specifically for COX-3 activity; broader COX activity may be inferred from prostaglandin metabolite levels in certain contexts, but patient selection is rarely COX-3–specific
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