PF-249

一种AMPKβ1异源三聚体的别构激活剂，对人AMPK α1β1γ1和α2β1γ1的EC50值分别为8nM和6nM。该激活剂在40µM时对AMPK α1β1γ1和α2β1γ1的选择性优于AMPK α1β2γ1、α2β2γ1和α2β2γ3，并且在10µM时对一系列受体、通道和磷酸二酯酶具有选择性。此外，该激活剂能够以剂量依赖的方式减少肥胖ZSF1大鼠模型中的蛋白尿并改善肾功能。An allosteric activator of AMPKβ1 heterotrimers (EC50s = 8 and 6 nM for human AMPK α1β1γ1 and -α2β1γ1, respectively); selective for AMPK α1β1γ1 and α2β1γ1 over AMPK α1β2γ1, -α2β2γ1, and -α2β2γ3 at 40 µM and a panel of receptors, channels, and phosphodiesterases at 10 µM; decreases proteinuria and improves kidney function in an obese ZSF1 rat model of diabetic nephropathy in a dose-dependent manner.分子式C17H16ClN3O3分子量345.8O=C(C1=CNC2=C1C=C(C3=C(OC)N=C(N(C)C)C=C3)C(Cl)=C2)O