BMS-687453

SKU: orb1227187

Description

A potent and selective PPARα agonist with EC50 of 10 nM for human PPARα and 410-fold selectivity over human PPARγ in PPAR-GAL4 transactivation assays; has negligible cross-reactivity against a panel of human nuclear hormone receptors including PPARδ; demonstrates an excellent pharmacological and safety profile for the treatment of atherosclerosis and dyslipidemia.Dyslipidemia Preclinical

Key Properties

• CAS Number: 1000998-59-3
• MW: 444.8649
• Purity: >98% (HPLC)
• Formula: C₂₂H₂₁ClN₂O₆
• SMILES: O=C(O)CN(CC1=CC=CC(OCC2=C(C)OC(C3=CC=C(Cl)C=C3)=N2)=C1)C(OC)=O
• Target: PPAR
• Solubility: DMSO: ≥ 31 mg/mL

Bioactivity

• 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. BMS-687453 induces PDK4 mRNA in the liver, with ED50 value of 0.24 mg/kg. 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.
• 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

BMS687453 | BMS 687453

Quick Database Links

Gene Symbol

PPAR