Microsomal prostaglandin E2 synthase-1 (mPGES-1) and 5-lipoxygenase (5-LO) are key enzymes in the synthesis of PGE2 and leukotrienes (LTs), respectively. PGE2 and LTs are bioactive lipids that contribute to a broad range of pathologies, including inflammation and various forms of cancer. Pirinixic acid aminothiazole is a dual inhibitor of mPGES-1 and 5-LO (IC50s = 0.4 and 0.2 μM, respectively). It is a weak inhibitor of COX-1 and -2 and has no effect on 12- and 15-LO isoforms. Pirinixic acid aminothiazole reduces the synthesis of PGE2 and LTC4 during zymosan-induced peritonitis in mice, resulting in a significantly diminished inflammatory response.
