The peroxisome proliferator-activated receptor alpha (PPARα) is a transcription factor that regulates hepatic fatty acid metabolism. GW 6471 is a potent PPARα antagonist with an IC50 value of 0.24μM.[1] The application of GW6471 (1×10-5mol/L) prevented embryoid bodies from cardiomyocyte differentiation and reduced the expression of α-actinin and troponin-T. GW6471 treatment also tended to decrease the levels of α-MHC and MLC2v in embryoid bodies compared with the controls.[2] Administration of GW 6471 (4 and 10μg/mouse, via intracerebroventricular route; or 1mg/kg, via intraperitoneal route) prevented the anticonvulsant effect of docosahexaenoic acid and the increase in seizure threshold in mice in a dose-dependent manner.[3]
作用机制
GW6471 is a PPARα antagonist. It disrupts the interactions between PPARα and its coactivators, such as steroid receptor coactivator-1 and CREB-binding protein, but promotes the binding of the co-repressors, such as silencing mediator for retinoid and thyroid hormone receptors and nuclear co-repressor.[1]
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