Microsomal prostaglandin E2 synthase-1 (mPGES-1), with cyclooxygenase-2 (COX-2), synthesizes PGE2, which is directly involved in signaling during inflammation, fever, and pain. 5-Lipoxygenase (5-LO) initiates the synthesis of leukotrienes (LTs), which are pro-inflammatory mediators. YS-121 is a dual inhibitor of mPGES-1 (IC50 = 3.9 μM) and 5-LO (IC50 = 4.1 μM). It effectively inhibits PGE2 and LT synthesis in both cell free and intact cell assays. Moreover, YS-121 (1.5 mg/kg, intraperitoneal) reduced pleural levels of PGE2 and LTB4 while blocking exudate formation and leukocyte infiltration in carrageenan-induced rat pleurisy. YS-121 has minor effects on COX-1 and COX-2, inhibiting these enzymes 24.8% and 38%, respectively, at 10 μM.
