Microsomal prostaglandin E2 synthase-1 (mPGES-1)

Microsomal prostaglandin E2 synthase-1 (mPGES-1) is an inducible, membrane-associated enzyme that catalyzes the conversion of prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2), a lipid mediator with central roles in inflammation, pain, fever, and several pathological conditions including cancer and cardiovascular disease[3][4][5][7]. mPGES-1 is a member of the MAPEG superfamily and is distinct from one constitutive isoform (mPGES-2) and a cytosolic form (cPGES). Unlike the constitutively expressed forms, mPGES-1 expression is strongly upregulated by proinflammatory stimuli, making it a critical terminal enzyme in the prostaglandin biosynthetic pathway during inflammation[4][7]. Selective inhibition of mPGES-1 has emerged as a promising strategy to modulate pathological PGE2 without some of the off-target side effects seen with upstream cyclooxygenase inhibitors[3][5]. mPGES-1 has been structurally characterized, and its activity is glutathione-dependent and tightly regulated in inflammatory states; however, no mPGES-1 inhibitor has reached the clinic due to unresolved concerns such as safety and efficacy translation from preclinical models[3][5].

Other names

Prostaglandin E synthase 1PTGESmPGES1PGES-1Membrane-associated prostaglandin E synthase-1MAPEG family member (context-dependent)

Specific mPGES-1 inhibitors reduce PGE2 synthesis by blocking the conversion of prostaglandin H2 to prostaglandin E2. Unlike COX inhibitors, mPGES-1 inhibitors selectively reduce PGE2 while sparing other prostanoids (such as prostacyclin and thromboxane), which might result in fewer side effects[3][5][9]