D4476 is a potent, selective, and cell-permeant CK1 (casein kinase 1) inhibitor with IC50 of 200 nM and 300 nM in a cell-free assay for CK1 from Schizosaccharomyces pombe and CK1δ, respectively. Also acts as an ALK5 inhibitor with IC50 of 500 nM.
D4476 is a dual inhibitor of both ALK5 with IC50 value of 94nM, and CK1 with IC50 values of 200nM and 300nM for CK1 and CK1δ from S. pombe, respectively[1][2]. D4476 inhibited TGF-β1-induced (FN) mRNA formation in A498 cells with IC50 value of 0.05μM and significantly reduced the TGF-β1-induced nuclear accumulation of Smad proteins with an IC50 value of 0.04 µM[1]. D4476 dose-dependently inhibited the phosphorylation of FOXO1a induced by insulin at Ser322 and Ser325 at concentration ranging in 25-150μM in H4IIE cells, but not the phosphorylation of Thr24, Ser256, Ser319 catalyzed by PKB, or the constitutively phosphorylated Ser329. Prior treatment with 150μM D4476 reduced the IGF-1 and serum-induced nuclear exclusion of FOXO1a to about 3 fold. This retarding of nuclear exclusion by D4476 may due to the acceleration of nuclear export[2].
作用机制
D4476 is an ATP-competitive inhibitor of CK1.
D4476 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
A375 cells
10-80 μM
Function assay
48 h
Inhibition of CK1-MDM2 complex in human A375 cells assessed as increase in p21 protein level at 10 to 80 uM after 48 hrs by immunoblotting analysis
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