Prostaglandin E2 synthase (PGES)

Prostaglandin E2 synthase refers to a group of enzymes that catalyze the terminal step in the biosynthesis of prostaglandin E2 (PGE2) from prostaglandin H2 (PGH2). In mammals, three main isoforms are recognized: microsomal prostaglandin E2 synthase-1 (mPGES-1), which is inducible and associated with inflammation, microsomal prostaglandin E2 synthase-2 (mPGES-2), and cytosolic prostaglandin E2 synthase (cPGES), both of which are constitutively expressed. mPGES-1 is of particular therapeutic interest as it is upregulated by inflammatory stimuli and functionally coupled to COX-2. Blocking PGES, especially mPGES-1, offers potential anti-inflammatory and anti-tumor effects with a potentially more favorable safety profile compared to traditional COX-2 inhibitors. The enzyme is involved in diverse physiological processes, including modulation of immune responses, fever, smooth muscle function, and blood flow, and has been implicated in various pathological conditions such as inflammation, cancer, neurological diseases, and cardiovascular dysfunction.

Other names

Prostaglandin E synthasePGESMembrane-associated prostaglandin E synthase-1 (mPGES-1)Membrane-associated prostaglandin E synthase-2 (mPGES-2)Cytosolic prostaglandin E synthase (cPGES)

PGES inhibitors block the conversion of PGH2 to PGE2, thereby reducing PGE2 levels and attenuating the downstream biological effects linked to inflammation, pain, and tumor progression. Differ from COX inhibitors by possibly avoiding some cardiovascular risks while reducing PGE2.