| Identification | Back Directory | [Name]
GW 6471 | [CAS]
880635-03-0 | [Synonyms]
GW 6471
GW 6471 USP/EP/BP
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
Propanamide, N-[(2S)-2-[[(1Z)-1-methyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propen-1-yl]amino]-3-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]propyl]-
[(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 | [Molecular Formula]
C35H36F3N3O4 | [MDL Number]
MFCD07784503 | [MOL File]
880635-03-0.mol | [Molecular Weight]
619.67 |
| Questions And Answer | Back Directory | [Uses]
GW 6471 is a potent antagonist of PPARα with IC50 of 0.24 μM. | [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 |
| Chemical Properties | Back Directory | [density ]
1.204±0.06 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
DMSO: 15 mg/mL
| [form ]
solid
| [pka]
15.90±0.46(Predicted) | [color ]
off-white
|
| Hazard Information | Back Directory | [General Description]
GW6471 prevents apoptosis and cell cycle arrest at G0/G1 in renal cell carcinoma. It reduces enhanced fatty acid oxidation and oxidative phosphorylation associated with glycolysis inhibition. | [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. | [in vivo]
To test the antitumor activity of PPARα antagonism in vivo, a subcutaneous xenograft mouse model is used. Caki-1 cells are implanted subcutaneously in nude (Nu/Nu) mice. After tumor masses reach ～5 mm in diameter, GW6471 is administrated intraperitoneally every other day for 4 wk at a dose (20 mg/kg mouse body wt) that is described to be effective in an in vivo dose-response study and confirmed here to be efficacious. There are significant differences in tumor growth between vehicle- and GW6471-treated animals. No toxicity is observed at the doses of GW6471 based on weights of the animals, and laboratory values, including kidney and liver function tests, are not adversely affected. To demonstrate on-target effects of GW6471, c-Myc levels are evaluated in the tumors, which show significant decreases in the GW6471-treated animals[3]. | [IC 50]
PPARα | [storage]
Store at +4°C |
|
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Sigma-Aldrich
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