Prostaglandin-endoperoxide synthase 3 (COX-3)

Prostaglandin-endoperoxide synthase 3 (commonly known as cyclooxygenase-3 or COX-3) is a splice variant of the cyclooxygenase family first described as a third isozyme after COX-1 and COX-2. It is encoded by an alternative transcript of the PTGS1 (COX-1) gene, retaining an intron not present in COX-1. In some species, such as dogs, this results in a functional enzyme that can be inhibited by drugs like acetaminophen and certain NSAIDs, playing a role in pain and fever regulation. However, in humans, this isoform is not functional—the splicing event causes a frameshift and produces a protein lacking cyclooxygenase activity, thus it does not contribute to prostaglandin synthesis or known physiological processes[1][3][5][7][9]. While COX-3 inhibitors are conceptually attractive as novel analgesic and antipyretic therapeutics in animals, the enzyme is not a viable drug target in humans, and its biological and clinical relevance in human disease is essentially negligible[1][3][5][7][9]. Note: - The term "Prostaglandin-endoperoxide synthase 3" (COX-3) is often misapplied in human biology, as there is no functional third COX enzyme in humans[1][3]. Some literature and databases may incorrectly list PTGS3 as a gene symbol; the correct state is that humans do not express a functional PTGS3 gene or protein[1][3][9]. - Most therapeutic targeting of cyclooxygenases in humans is limited to COX-1 (PTGS1) and COX-2 (PTGS2)[4][5][8].

Other names

Cyclooxygenase-3PTGS3 (informal, see below)COX-3

Inhibition of COX activity (where functional, e.g. in dogs/rodents) reduces prostaglandin synthesis, providing analgesic and antipyretic effects (e.g. acetaminophen inhibition in CNS)[3][9][7]