Microsomal prostaglandin E synthase-1 (mPGES-1) converts the COX product prostaglandin H2 (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. PF-9184 is a potent inhibitor of mPGES-1 (IC50 = 16.5 nM for recombinant human enzyme). It displays at least 6,500-fold selectivity for mPGES-1 over COX-1 and COX-2. PF-9184 blocks the synthesis of PGE2 in LPS-treated human whole blood and in IL-1β-stimulated fibroblasts (IC50s = 0.4-5 μM).
