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

Prostaglandin-endoperoxide synthase 1 (COX-1) is a constitutively expressed enzyme that catalyzes the conversion of arachidonic acid into prostaglandin H2 (PGH2), the precursor for various prostanoids including thromboxane A2 (TXA2) [1, 4]. In platelets, COX-1 is the dominant isoform and is essential for TXA2-mediated platelet aggregation and vasoconstriction [2, 3]. Because mature platelets lack a nucleus, they are unable to regenerate the enzyme once it is inhibited; this makes platelet COX-1 a unique pharmacological target for long-lasting antiplatelet therapy [2]. Low-dose aspirin is the most prominent drug targeting this enzyme, acting via irreversible acetylation of a serine residue in the active site, thereby preventing cardiovascular events like myocardial infarction [2, 5]. However, COX-1 also plays a protective role in the gastrointestinal tract by promoting the synthesis of cytoprotective prostaglandins [3]. Consequently, systemic inhibition of COX-1 is associated with side effects such as gastric mucosal injury and increased bleeding risk [2, 3].

Other names

PTGS1Cyclooxygenase-1Prostaglandin G/H synthase 1PGH synthase 1COX1

Inhibition of the cyclooxygenase active site of the enzyme, which prevents the conversion of arachidonic acid to prostaglandin H2 (PGH2). In platelets, this specifically blocks the synthesis of thromboxane A2 (TXA2), a key mediator of aggregation [1, 2, 4].