Prostaglandin-endoperoxide synthase 1 and 2 (COX-1 and COX-2) (COX-1 and COX-2)

Cyclooxygenase-1 (COX-1) and Cyclooxygenase-2 (COX-2), also known as prostaglandin-endoperoxide synthases 1 and 2, are bifunctional enzymes that catalyze the rate-limiting step in the conversion of arachidonic acid to prostanoids, including prostaglandins, prostacyclin, and thromboxane [1, 2]. COX-1 is constitutively expressed in most tissues and is essential for maintaining homeostatic functions such as gastric mucosal integrity, renal blood flow, and platelet aggregation [3]. COX-2 is typically undetectable in most resting tissues but is rapidly induced by inflammatory stimuli, cytokines, and growth factors, playing a central role in pain, fever, and inflammation [4]. These enzymes are the primary therapeutic targets for nonsteroidal anti-inflammatory drugs (NSAIDs), which are used to treat conditions ranging from acute pain to chronic inflammatory diseases like rheumatoid arthritis [3, 5]. While non-selective NSAIDs inhibit both isoforms, selective COX-2 inhibitors were designed to minimize gastrointestinal toxicity, though they have been associated with an increased risk of cardiovascular events due to the suppression of prostacyclin without affecting thromboxane [4, 6]. Beyond inflammation, these enzymes are implicated in cancer progression, particularly colorectal cancer, where COX-2 is often overexpressed [2]. Therapeutic strategies involving these targets must balance anti-inflammatory efficacy with potential renal, gastric, and cardiovascular toxicities [3].

Other names

PTGS1PTGS2Cyclooxygenase-1Cyclooxygenase-2PGH synthase 1PGH synthase 2Prostaglandin G/H synthase 1Prostaglandin G/H synthase 2

Inhibition of the cyclooxygenase active site, preventing the conversion of arachidonic acid to prostaglandin H2 (PGH2) [3, 4].