LY2562175

LY2562175 is a potent and selective FXR agonist, with an EC₅₀ of 193 nM^[1]. IC50 & Target: EC50: 193 nM (FXR) In Vitro: LY2562175 promotes transcriptional activation of human FXR in a cell-based co-transfection assay with an EC₅₀ of 193 nM. LY2562175 promotes recruitment of a peptide from the nuclear receptor interaction domain of the coactivator SRC-1 with a relative EC₅₀ of 121 nM and 93.5% efficacy as compare to GW4064^[1]. In Vivo: LY2562175 causes a dose-dependent decrease in serum cholesterol and serum triglycerides. At a dose of 10 mg/kg, the decrease in cholesterol with LY2562175 is 80% below vehicle-treated animals, and the decrease in serum triglycerides is 76% from control group. The ED₅₀ for serum cholesterol is determined to be 2 and 3.4 mg/kg for serum triglycerides. Treatment of female ZDF rats with LY2562175 results in a dose dependent lowering of plasma triglycerides in the fasted and nonfasted states. When administered as a fixed dose combination with BRL49653, LY2562175 further lowers fasted and nonfasted plasma triglycerides. FPLC fractionation of the lipoproteins reveals that LY2562175 treatment results in a reduction in vLDL-C and a dramatic increase in HDL-c in this animal model^[1].