AVE-8134 is an agonist of PPARα. For human and rodent PPARα receptor, the EC50 values are 100 and 3000 nM, respectively.

PPARα:100 nM （EC50）（ Human PPARα)

AVE8134 is a full PPARα dominated PPAR agonist, but not active on PPARδ[1]. In monocytes, AVE8134 (10 μM) increases the expression of CD36 and the macrophage scavenger receptor 1, resulting in enhanced uptake of oxidized LDL[2]. In HUVEC, AVE8134 (1 μM) increases Ser-1177-eNOS phosphorylation but not eNOS expression.

AVE8134 reduces phenylephrine-induced hypertrophy in adult rat cardiomyocytes[2]. Treatment at AVE8134 decreases plasma proBNP and arginine and increases plasma citrulline and urinary NOx/creatinine ratio. In female ZDF rats, AVE8134 (3-30 mg/kg/d for 2 weeks) improves insulin-sensitivity index. In post-MI rats, AVE8134 (3 mg/kg and 10 mg/kg) dose-dependently improves cardiac output, myocardial contractility and relaxation and reduces lung and left ventricular weight and fibrosis. In DOCA rats, AVE8134 (3 mg/kg/d) prevents development of high blood pressure, myocardial hypertrophy and cardiac fibrosis, and ameliorates endothelial dysfunction. In pre-diabetic male ZDF rats, AVE8134 (10 mg/kg/d for 8 weeks) produces an anti-diabetic action comparable to rosiglitazone, without the PPARγ mediated adverse effects on body weight and heart weight. In male ZDF rats, AVE8134 (20 mg/kg/d for 12 weeks) increases mRNA levels of the target genes LPL and PDK4 about 20 fold in the liver, and there is no relevant effect with rosiglitazone[1]. AVE8134 (0.3 mg/kg/d) improves cardiac and vascular function and increases life expectancy without lowering blood pressure. In old SHR, treatment with a low dose of In female hApo A1 mice, AVE8134 (130 mg/kg/d, po for 12 d) dose-dependently loweres the plasma triglycerides, and increases the serum HDL-cholesterol, hApo A1 and mouse Apo E levels.