A review on mPGES-1 inhibitors: From preclinical studies to clinical applications

Prostaglandin E₂ (PGE₂) is a lipid mediator of inflammation and cancer progression. It is mainly formed via metabolism of arachidonic acid by cyclooxygenases (COX) and the terminal enzyme microsomal prostaglandin E synthase-1 (mPGES-1). Widely used non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX activity, resulting in decreased PGE₂ production and symptomatic relief. However, NSAIDs block the production of many other lipid mediators that have important physiological and resolving actions, and these drugs cause gastrointestinal bleeding and/or increase the risk for severe cardiovascular events. Selective inhibition of downstream mPGES-1 for reduction in only PGE₂ biosynthesis is suggested as a safer therapeutic strategy. This review covers the recent advances in characterization of new mPGES-1 inhibitors in preclinical models and their future clinical applications.