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 functions as a complete PPARα-dominant PPAR agonist, while exhibiting no activity towards PPARδ. At a concentration of 10 μM, it augments the expression of CD36 and macrophage scavenger receptor 1 in monocytes, facilitating the accelerated uptake of oxidized LDL. Additionally, in HUVEC at 1 μM, AVE8134 boosts Ser-1177-eNOS phosphorylation without affecting eNOS expression.

AVE8134 effectively reduces heart cell enlargement caused by phenylephrine in adult rat cardiomyocytes and modulates various biochemical markers, decreasing plasma proBNP and arginine, while increasing plasma citrulline and the urinary NOx/creatinine ratio. It enhances insulin sensitivity in female ZDF rats at doses of 3-30 mg/kg/d over two weeks, and at doses of 3 mg/kg and 10 mg/kg, it dose-dependently ameliorates cardiac output, myocardial contractility and relaxation, and diminishes lung and left ventricular weight and fibrosis in post-myocardial infarction rats. Furthermore, AVE8134 at 3 mg/kg/d inhibits the onset of high blood pressure, heart enlargement, and cardiac fibrosis, and improves endothelial function in DOCA rats. In pre-diabetic male ZDF rats, a dose of 10 mg/kg/d for eight weeks shows anti-diabetic effects comparable to rosiglitazone but without adverse impacts on body and heart weight linked to PPARγ activation. At a dosage of 20 mg/kg/d for twelve weeks in male ZDF rats, AVE8134 significantly raises mRNA levels of LPL and PDK4 genes in the liver, a response not observed with rosiglitazone. Additionally, a minimal dosage of 0.3 mg/kg/d enhances cardiac and vascular functions and extends life expectancy without affecting blood pressure. In elderly SHR rats, a low dose improves cardiovascular health, and in female hApo A1 mice, 130 mg/kg/d administered orally for 12 days lowers plasma triglycerides and increases serum HDL-cholesterol, hApo A1, and mouse Apo E levels in a dose-dependent manner.