A MEK inhibitor and AMPK activator
U-0126 is a MEK inhibitor with IC50 values of 72 nM and 58 nM for MEK1 and MEK2, respectively. [1] It is noncompetitive with respect adenosine triphosphate (ATP) and its phosphorylation target ERK and it shows little to no inhibition against a number of other kinases including PKC, Ab1, Raf, MEKK, ERK, JNK, MKK-3, MKK-4, MKK-6, Cdk2, and Cdk4. However, U-0126 does phosphorylate and activate AMP-activated protein kinase (AMPK) in a dose-dependent manner (EC50 = 15 µM in HEK293 cells).[2]? It increases the ratios of ADP to ATP and AMP to ATP and increases phosphorylation of the AMPK target acetyl-CoA carboxylase (ACC).
U-0126是一种MEK抑制剂，其对MEK1和MEK2的IC50值分别为72 nM和58 nM。[1] 它在ATP和其磷酸化靶点ERK方面呈非竞争性，而且在其他许多激酶中几乎不表现出抑制作用，包括PKC、Ab1、Raf、MEKK、ERK、JNK、MKK-3、MKK-4、MKK-6、Cdk2和Cdk4。然而，U-0126以剂量依赖的方式在HEK293细胞中磷酸化并激活AMP-activated protein kinase（AMPK）（EC50 = 15μM）[2]。它增加了ADP / ATP和AMP / ATP比率，并增加了AMPK靶点乙酰辅酶A羧化酶（ACC）的磷酸化。
Reference:
[1]. Favata, M.F., Horiuchi, K.Y., Manos, E.J., et al. Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J. Biol. Chem. 273(29), 18623-18632 (1998).
[2]. Dokladda, K., Green, K.A., Pan, D.A., et al. PD98059 and U0126 activate AMP-activated protein kinase by increasing the cellular AMP:ATP ratio and not via inhibition of the MAP kinase pathway. FEBS Lett. 579(1), 236-240 (2005).
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