BMS-687453

BMS-687453 is a potent and selective PPARα agonist, with an EC₅₀ and IC₅₀ of 10 nM and 260 nM for human PPARα and 4100 nM and >15000 nM for PPARγ in PPAR-GAL4 transactivation assays. IC50 & Target: EC50: 10 nM (GAL4-human PPARα), 4100 nM (GAL4-human PPARγ)^[1]
IC50: 260 nM (Human PPARα), >15000 nM (Human PPARγ)^[1]
In Vitro: BMS-687453 is a potent and selective PPARα agonist, with an EC₅₀ and IC₅₀ of 10 nM and 260 nM for human PPARα and ∼410-fold and more than 57-fold selectivity vs human PPARγ of 4100 nM and >15000 nM in PPAR-GAL4 transactivation assays. BMS-687453 exhibits high PPARα potency (EC₅₀ = 47 nM) with ∼50-fold selectivity vs PPARγ (EC₅₀ = 2400 nM) in HepG2 cells. However, BMS-687453 shows less potent activities in rodent PPARα functional assays, with a moderate EC₅₀ of 426 nM for mouse and 488 nM for hamster but remains a full PPARα agonist in both species^[1]. In Vivo: BMS-687453 (10, 50, 100, p.o.) dose-dependently increases serum ApoA1 protein levels and low-density lipoprotein-cholesterol (LDLc) levels in mice. BMS-687453 (1, 3, 10 mg/kg, p.o.) decreases HDLc levels in high fat-fed hamsters^[1]. BMS-687453 induces PDK4 mRNA in the liver, with ED₅₀ value of 0.24 mg/kg^[2]. BMS-687453 (300 mg/kg, p.o.) causes skeletal myofiber degeneration and necrosis characterized by observed discoid changes, myofibril lysis, hyalinization, and cellular infiltration in male rats. BMS-687453 (300 mg/kg, p.o.) induces a mild toxicity in both fast and slow-twitch muscles in male rats^[3].