Prostaglandin E2 (PGE2) is the major PG synthesized at sites of inflammation and plays an important role in different inflammatory diseases. It acts as a mediator of pain and inflammation and promotes bone destruction. The increased synthesis of PGE2 during inflammation can be accounted for by increased expression of both cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1).[1],[2],[3] CAY10526 is an inhibitor of PGE2 production through the selective modulation of mPGES-1 expression. It dose-dependently inhibits PGE2 production in lipopolysaccharide-stimulated RAW 264.7 cells with an IC50 value of 1.8 μM without any effect on COX-2 expression.[4]

Reference:
[1]. Claveau, D., Sirinyan, M., Guay, J., et al. Microsomal prostaglandin E synthase-1 is a major terminal synthase that is selectively up-regulated during cyclooxygenase-2-dependent prostaglandin E2 production in the rat adjuvant-induced arthritis model. Journal of Immunology 170, 4738-4744 (2003).
[2]. Guay, J., Bateman, K., Gordon, R., et al. Carrageenan-induced paw edema in rat elicits a predominant prostaglandin E2 (PGE2) response in the central nervous system associated with the induction of microsomal PGE2 synthase-1. The Journal of Biological Chemisty 279(23), 24866-24872 (2004).
[3]. Stichtenoth, D.O., Thorén, S., Bian, H., et al. Microsomal prostaglandin E synthase is regulated by proinflammatory cytokines and glucocorticoids in primary rheumatoid synovial cells. Journal of Immunology 167, 469-474 (2001).
[4]. Guerrero, M.D., Aquino, M., Bruno, I., et al. Synthesis and pharmacological evaluation of a selected library of new potential anti-inflammatory agents bearing the γ-hydroxybutenolide scaffold: a new class of inhibitors of prostanoid production through the selective modulation of microsomal prostaglandin E synthase-1 expression. Journal of Medicinal Chemistry 50, 2176-2184 (2007).