Microsomal prostaglandin E synthase-2 (mPGES-2)

Microsomal prostaglandin E synthase-2 (mPGES-2), encoded by the PTGES2 gene, is a membrane-associated isomerase that plays a key role in the arachidonic acid cascade by converting prostaglandin H2 (PGH2) into prostaglandin E2 (PGE2) [1, 6]. Unlike the highly inducible mPGES-1, mPGES-2 is constitutively expressed in various tissues, including the liver, kidney, heart, and brain [9, 11]. Its biological role is multifaceted; while it functions as a PGE2 synthase in vitro, evidence suggests that in vivo, it may primarily act as a lyase to degrade PGH2 into 12(S)-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and malondialdehyde (MDA) when complexed with heme [1, 10]. mPGES-2 is implicated in the pathogenesis of several diseases, including colorectal cancer, non-alcoholic fatty liver disease (NAFLD), and metabolic disorders such as diabetes [4, 6, 7]. Targeting mPGES-2 is considered a potential therapeutic strategy to modulate inflammation and tumor progression with a potentially improved safety profile compared to traditional non-steroidal anti-inflammatory drugs (NSAIDs) [4, 12]. Although specific clinical candidates are limited, experimental inhibitors such as 2-chloromethylquinoline and various natural compounds like prenylated chalcones have shown promise in preclinical models [4, 6].

Other names

Prostaglandin E synthase 2PTGES2PGES2C9orf15GBF-1GBF1Membrane-associated prostaglandin E synthase 2

Inhibition of the enzymatic conversion of prostaglandin H2 to prostaglandin E2, thereby reducing the levels of the pro-inflammatory mediator PGE2.