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

Prostaglandin-endoperoxide synthase 2, commonly known as Cyclooxygenase 2 (COX-2), is a key enzyme responsible for converting arachidonic acid into prostaglandin H2, a precursor for various pro-inflammatory mediators (UniProt P35354). Unlike the constitutively expressed COX-1, COX-2 is an inducible enzyme whose expression is typically low but rapidly increases in response to cytokines, growth factors, and inflammatory stimuli (StatPearls, NCBI Gene ID 5743). This enzyme plays a central role in mediating pain, fever, and inflammation, making it a primary therapeutic target for nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors known as coxibs (StatPearls). Beyond inflammation, COX-2 is frequently overexpressed in various malignancies, particularly colorectal cancer, where it contributes to tumor cell proliferation, angiogenesis, and resistance to apoptosis (PubMed, Cancer Metastasis Rev. 2004). However, the use of selective COX-2 inhibitors is associated with significant safety concerns, most notably an increased risk of serious cardiovascular events like myocardial infarction and stroke (FDA, Celebrex Label). These risks are thought to stem from an imbalance between the inhibition of vasodilatory prostacyclin and the continued production of pro-thrombotic thromboxane A2 (Iranian Journal of Pharmaceutical Research, 2011). Additionally, COX-2 inhibition can lead to renal complications such as fluid retention and hypertension due to its role in maintaining renal blood flow (StatPearls).

Other names

PTGS2PHS-2Prostaglandin G/H synthase 2Cyclooxygenase-2Cycloxygenase 2

Inhibition of the cyclooxygenase active site of the enzyme, preventing the conversion of arachidonic acid to prostaglandin H2 (PGH2), which is the common precursor for pro-inflammatory prostaglandins and thromboxanes.