Prostaglandin E synthase (PTGES) (PTGES)

Prostaglandin E synthase (PTGES), specifically the microsomal form mPGES-1, is a glutathione-dependent terminal enzyme in the arachidonic acid cascade [UniProt P23219]. It catalyzes the conversion of prostaglandin H2 (PGH2), produced by cyclooxygenases (COX-1 and COX-2), into prostaglandin E2 (PGE2), which is a potent mediator of inflammation, pain, and fever [NCBI Gene 9536]. While PTGES is expressed at low levels in most tissues, it is highly inducible by inflammatory stimuli such as interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) [Frontiers in Pharmacology, 2020]. In pathological states, PTGES is often overexpressed alongside COX-2, leading to excessive PGE2 production associated with rheumatoid arthritis, osteoarthritis, and various cancers [Therapeutic Advances in Musculoskeletal Disease, 2015]. Pharmacological inhibition of PTGES is an active area of drug development, aiming to provide the anti-inflammatory and analgesic benefits of NSAIDs while minimizing side effects like gastrointestinal toxicity and cardiovascular risks by sparing other beneficial prostanoids like prostacyclin [British Journal of Pharmacology, 2019]. Several small-molecule inhibitors, such as LY3023703 and GRC-27864, have entered clinical trials for pain and inflammatory conditions [ClinicalTrials.gov]. The strategy of targeting PTGES is intended to avoid the "prostanoid shunting" and cardiovascular imbalances often associated with traditional COX inhibitors.

Other names

Microsomal prostaglandin E synthase-1mPGES-1MGST1-L1MGST1L1Glutathione S-transferase 1-like 1p53-induced gene 12 proteinPIG12TP53I12

Selective inhibition of the microsomal prostaglandin E synthase-1 enzyme, which catalyzes the isomerization of prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2).