COX

Cyclooxygenase (COX) catalyzes the conversion of arachidonic acid into prostaglandin G₂ and prostaglandin H₂, initiating prostanoid biosynthesis that regulates inflammation, vascular homeostasis, pain signaling, and tissue responses to injury^[1][2]. Mechanistically, COX enzymes contain two major isoforms, COX-1 and COX-2, which catalyze the same biochemical reaction but differ in gene regulation, tissue distribution, intracellular localization, and substrate selectivity^[1][2]. COX-1 is constitutively expressed in most tissues and contributes to gastric mucosal protection, platelet function, and renal hemodynamic maintenance, whereas COX-2 is rapidly induced by inflammatory cytokines, growth factors, and pathological stimuli^[1][3]. In disease models, increased COX-2 expression is associated with chronic inflammatory disorders, neurodegenerative diseases, and multiple cancer types, supporting its central role in inflammation-driven pathophysiology and tumor progression^[1][2]. Compared with related isoforms, COX-2 contains a larger and more flexible substrate-binding channel that enables distinct inhibitor selectivity and broader fatty-acid utilization^[1][4]. Therefore, selective and non-selective nonsteroidal anti-inflammatory drugs (NSAIDs) remain important experimental tools for dissecting prostaglandin-dependent signaling pathways, while COX-2-selective inhibitors have been widely used to investigate inflammatory mechanisms and disease-associated prostanoid production^[1][2][4].