Prostaglandin-endoperoxide synthase 2 (COX-2) (COX-2)

Prostaglandin-endoperoxide synthase 2, widely known as COX-2, is an inducible enzyme that catalyzes the rate-limiting step in the biosynthesis of prostaglandins from arachidonic acid [UniProt: P35354]. While its isoform COX-1 is constitutively expressed in most tissues for homeostatic functions like gastric protection, COX-2 expression is rapidly induced by inflammatory stimuli, cytokines, and growth factors [PubMed: 16007524]. This enzyme is a primary mediator of inflammation, pain, and fever, making it a major therapeutic target for nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors known as coxibs [StatPearls: COX-2 Inhibitors]. Beyond inflammation, COX-2 is frequently overexpressed in various malignancies, such as colorectal and breast cancers, where it contributes to tumor cell survival, angiogenesis, and metastasis [PubMed: 25850390]. Pharmacological inhibition of COX-2 reduces the production of pro-inflammatory mediators, providing relief in conditions like rheumatoid arthritis and osteoarthritis. However, the use of selective COX-2 inhibitors is clinically balanced against significant cardiovascular risks, primarily due to the suppression of cardioprotective prostacyclin (PGI2) without a corresponding reduction in pro-thrombotic thromboxane A2 (TXA2) [PubMed: 15754715]. This imbalance can lead to an increased incidence of thrombotic events, which led to the withdrawal of several drugs in this class from the market. Despite these concerns, COX-2 remains a vital target in pain management and is being investigated for its potential in cancer chemoprevention.

Other names

PTGS2Cyclooxygenase-2PHS-2Prostaglandin G/H synthase 2

Selective or non-selective inhibition of the cyclooxygenase active site, preventing the conversion of arachidonic acid to prostaglandin H2 (PGH2) [StatPearls: NSAIDs].