Microsomal prostaglandin E synthase-1 and -2 (mPGES-1/2)

Microsomal prostaglandin E synthase-1 (mPGES-1) and microsomal prostaglandin E synthase-2 (mPGES-2) are terminal enzymes in the arachidonic acid cascade that catalyze the conversion of prostaglandin H2 (PGH2) into prostaglandin E2 (PGE2) (NIH, 2021). mPGES-1 is an inducible enzyme that is significantly upregulated during inflammatory responses, often in coordination with cyclooxygenase-2 (COX-2), making it a primary target for anti-inflammatory and analgesic drug development (ACS, 2008; NIH, 2009). In contrast, mPGES-2 is constitutively expressed and contributes to physiological PGE2 production, though its role as a therapeutic target is less defined (Frontiers, 2011; NIH, 2011). Inhibition of these enzymes, particularly mPGES-1, is pursued as a strategy to reduce PGE2 levels in conditions like rheumatoid arthritis, osteoarthritis, and various cancers without the cardiovascular and gastrointestinal risks associated with traditional NSAIDs (NIH, 2011; ACS, 2016). Several small-molecule inhibitors, such as LY3023703 and MF63, have been developed to selectively target mPGES-1, while some traditional NSAIDs like indomethacin have been shown to interact with mPGES-2 (NIH, 2011; NIH, 2019). Therapeutic challenges include the potential shunting of the common substrate PGH2 toward other prostanoids like thromboxane and ensuring cross-species potency during drug development (NIH, 2019; TandfOnline, 2021). Overall, these synthases represent a critical node in lipid signaling with significant implications for inflammation, oncology, and neurodegeneration (BioWorld, 2022; NIH, 2021).

Other names

PTGESPTGES2Prostaglandin E synthase 1Prostaglandin E synthase 2mPGES-1mPGES-2

Inhibition of the terminal synthesis of prostaglandin E2 from the precursor prostaglandin H2 (NIH, 2021; NIH, 2011).