938069-71-7

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). 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.

CAY10526 is a specific microsomal PGE2 synthase-1 (mPGES1) inhibitor. CAY10526 inhibits PGE2 production through the selective modulation of mPGES1 expression but does not affect COX-2. CAY10526 significantly suppresses tumor growth and increases apoptosis in melanoma xenografts. CAY10526 reduces BCL-2 and BCL-XL (anti-apoptotic) protein levels and increases BAX and BAK (pro-apoptotic) as well as cleaved caspase 3 levels. CAY10526 inhibits cell viability (IC50<5 μM) in three melanoma cell lines expressing mPGES1[1].

[1] Sun-Hee Kim, et al. Microsomal PGE2 synthase-1 regulates melanoma cell survival and associates with melanoma disease progression. Pigment Cell Melanoma Res. 2016 May;29(3):297-308. DOI:10.1111/pcmr.12455