D4476

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Chemical Structure| 301836-43-1 同义名 : Casein Kinase I Inhibitor
CAS号 : 301836-43-1
货号 : A388816
分子式 : C23H18N4O3
纯度 : 99%
分子量 : 398.41
MDL号 : MFCD09037526
存储条件：

Pure form Sealed in dry,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(125.5 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
生物活性
靶点

  • CK1

    CK1δ, IC50:300 nM

    CK1 from Schizosaccharomyces pombe, IC50:200 nM
描述 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.
细胞研究
细胞系 浓度 检测类型 检测时间 活性说明 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 24007918
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.51mL

0.50mL

0.25mL

12.55mL

2.51mL

1.25mL

25.10mL

5.02mL

2.51mL
参考文献

[1]Callahan JF, Burgess JL, et al. Identification of novel inhibitors of the transforming growth factor beta1 (TGF-beta1) type 1 receptor (ALK5). J Med Chem. 2002 Feb 28;45(5):999-1001.

[2]Rena G, Bain J, et al. D4476, a cell-permeant inhibitor of CK1, suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a. EMBO Rep. 2004 Jan;5(1):60-5.