Description
Microsomal prostaglandin E
2 synthase-
1 (mPGES-
1), with cyclooxygenase-
2 (COX-
2), synthesizes PGE
2, 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 (IC
50 = 3.9 μM) and 5-
LO (IC
50 = 4.1 μM). It effectively inhibits PGE
2 and LT synthesis in both cell free and intact cell assays. Moreover, YS-121 (1.5 mg/kg, intraperitoneal) reduced pleural levels of PGE
2 and LTB
4 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.
Definition
ChEBI: Octanoic acid, 2-[[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]thio]- is a medium-chain fatty acid.
References
[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]. journal of medicinal chemistry, 2008, 51(24): 8068-8076.
[2] mehrotra s, morimiya a, agarwal b, et al. microsomal prostaglandin e2 synthase‐1 in breast cancer: a potential target for therapy[j]. the journal of pathology, 2006, 208(3): 356-363.werz o, greiner c, koeberle a, et al. novel and potent inhibitors of 5-lipoxygenase product synthesis based on the structure of pirinixic acid[j]. journal of medicinal chemistry, 2008, 51(17): 5449-5453.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]. journal of pharmacology and experimental therapeutics, 2010, 332(3): 840-848.
