880635-03-0

Basic information

• Product Name: GW 6471
• Synonyms: N-((2S)-2-(((1Z)-1-METHYL-3-OXO-3-(4-(TRIFLUOROMETHYL)PHENYL)PROP-1-ENYL)AMINO)-3-(4-(2-(5-METHYL-2-PHENYL-1,3-OXAZOL-4-YL)ETHOXY)PHENYL)PROPYL)PROPANAMIDE;[(2S)-2-[[(1Z)-1-METHYL-3-OXO-3-[4-(TRIFLUOROMETHYL)PHENYL]-1-PROPENYL]AMINO]-3-[4-[2-(5-METHYL-2-PHENYL-4-OXAZOLYL)ETHOXY]PHENYL]PROPYL]-CARBAMIC ACID ETHYL ESTER;GW 6471
• CAS NO: 880635-03-0
• Molecular Formula: C35H36F3N3O4
• Molecular Weight: 619.67
• Product Categories: Aromatics;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 880635-03-0.mol

Chemical Properties

• Appearance: off-white/solid
• Density: 1.204±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• Solubility: DMSO: 15 mg/mL
• PKA: 15.90±0.46(Predicted)
• CAS DataBase Reference: GW 6471(CAS DataBase Reference)
• NIST Chemistry Reference: GW 6471(880635-03-0)
• EPA Substance Registry System: GW 6471(880635-03-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 880635-03-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
GW 6471 is used as a PPARα antagonist for its ability to modulate the binding affinity of the PPARα ligand-binding domain to co-repressor proteins, which can have therapeutic implications in various diseases.
Used in Cancer Research:
GW 6471 is used as a research tool to study the effects of PPARα antagonism on apoptosis and cell cycle arrest in renal cell carcinoma, providing insights into potential therapeutic strategies for cancer treatment.
Used in Metabolic Studies:
GW 6471 is used as a research compound to investigate the role of PPARα in fatty acid oxidation and oxidative phosphorylation, contributing to a better understanding of metabolic pathways and their regulation.

In vitro

GW6471 completely inhibits GW409544-induced activation of PPARα with IC50 of 0.24 μM. GW6471 at concentration ranging from 0.001-10 μM disrupts the interactions between PPAR and coactivator motifs derived from SRC-1 or CBP, but promotes the binding of the co-repressor motifs from SMRT or N-CoR. GW6471 adopts a U-shaped configuration and wraps around C276 of helix 3, destroys the integrity of the charge clamp but leaves sufficient space to accommodate the additional helical turn of the co-repressor motif in the PPAR/GW6471/SMRT complexes. [1] GW6471 at concentration of 10 μM significantly prevents cardiomyocyte differentiation and results in the reduced expression of cardiac sarcomeric proteins (ie α-actinin, troponin-T) and specific genes (ie α-MHC, MLC2v) in a time-dependent manner through inhibiting PPARα.

Targets

PPARα

Biochem/physiol Actions

GW6471 is a PPARα antagonist, which completely inhibits GW409544-induced activation of PPARα with an IC50 = 0.24 μM. GW6471 induces a PPARα conformation that interacts efficiently with co-repressors.