| Description | BMS-687453 is a potent and selective PPAR alpha agonist, with an EC(50) of 10 nM for human PPARalpha and approximately 410-fold selectivity vs human PPARgamma in PPAR-GAL4 transactivation assays. |
| In vitro | BMS-687453 is 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 (10-100 mg/kg) reduces plasma triglyceride levels and increases HDL levels in human ApoA1 transgenic mice. It also reduces serum triglyceride and LDL levels in hamsters fed a high-fat diet[2] |
| Animal experiments | Male Syrian golden hamsters were acclimated to 12 h light/dark reverse light cycle for 7 days with high fat diet, then dosed daily by oral gavage for 21 days while on the same diet. At the end of the experiment, blood samples were drawn retro-orbitally after an 18 h fast and 24 h after the last dose for the determination of serum lipid levels. Livers were dissected out for mRNA analysis [1]. |
| Target activity | PPARα (human):260 nM |
| molecular weight | 444.86 |
| Molecular formula | C22H21ClN2O6 |
| CAS | 1000998-59-3 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 31 mg/mL (69.68 mM) |
| References | 1. Li J, et al. Discovery of an oxybenzylglycine based peroxisome proliferator activated receptor alpha selective agonist 2-((3-((2-(4-chlorophenyl)-5-methyloxazol-4-yl)methoxy)benzyl)(methoxycarbonyl)amino)acetic acid (BMS-687453). J Med Chem. 2010 Apr 8;53(7):2854-64. 2. Mukherjee R , Locke K T , Miao B , et al. Novel Peroxisome Proliferator-Activated Receptor ? Agonists Lower Low-Density Lipoprotein and Triglycerides, Raise High-Density Lipoprotein, and Synergistically Increase Cholesterol Excretion with a Liver X Receptor Agonist[J]. Journal of Pharmacology and Experimental Therapeutics, 2008, 327(3):716-726. |