Microsomal prostaglandin E synthase-1 (mPGES-1) converts the COX product PGH2 into the biologically active PGE2. Like COX-2, the expression of mPGES-1 is induced in response to pro-inflammatory mediators, including LPS, IL-1β, and TNF-α. CAY10678 is a benzoimidazole that potently inhibits human and rat recombinant mPGES-1 (IC50 = 0.09 and 0.9 μM, respectively). It has minimal effects on COX-1, COX-2, PGIS, and hematopoietic PGDS at 50 μM but reduces lipocalin-type PGDS activity by 60% at this concentration. CAY10678 dose-dependently blocks PGE2 synthesis in isolated cells and whole blood treated with LPS or IL-1β. It also dose-dependently reduces PGE2 synthesis and cell recruitment during inflammation in mice.
