YS-121

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)¹ and 5-LO (IC₅₀ = 4.1 μM).² 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.³ YS-121 has minor effects on COX-1 and COX-2, inhibiting these enzymes 24.8% and 38%, respectively, at 10 μM.¹

WARNING This product is not for human or veterinary use.

1. Koeberle, A., Zettl, H., Greiner, C., et al. Pirinixic acid derivatives as novel dual inhibitors of microsomal prostaglandin E₂ synthase-1 and 5-lipoxygenase. J. Med. Chem. 51(24), 8068-8076 (2008).

2. Werz, O., Greiner, C., Koeberle, A., et al. Novel and potent inhibitors of 5-lipoxygenase product synthesis based on the structures of pirinixic acid. J. Med. Chem. 51(17), 5449-5453 (2008).

3. Koeberle, A., Rossi, A., Zettl, H., et al. The molecular pharmacology and in vivo activity of 2-(4-chloro-6-(2,3-dimethylphenylamino)pyrimidin-2-ylthio)octanoic acid (YS121), a dual inhibitor of microsomal prostaglandin E₂ synthase-1 and 5-lipoxygenase. J. Pharmacol. Exp. Ther. 332(3), 840-848 (2010).