CCT251545 是一种有效的、具有口服活性的WNT抑制剂，在 7dF3 细胞中对 WNT 抑制作用的IC50值为 5 nM。它是选择性化学探针，用于探索 CDK8 和 CDK19 在人类疾病中的作用。

CCT251545 is an potent and oral-bioavailable WNT signaling inhibitor(IC50 of 5 nM in 7dF3 cells).

CCT251545, a small-molecule inhibitor of the WNT pathway discovered through cell-based screening, is a potent and selective chemical probe for the human Mediator complex-associated protein kinases CDK8 and CDK19 with >100-fold selectivity over 291 other kinases.?X-ray crystallography demonstrates a type 1 binding mode involving insertion of the CDK8 C terminus into the ligand binding site.?In contrast to type II inhibitors of CDK8 and CDK19, CCT251545 displays potent cell-based activity.?We show that CCT251545 and close analogs alter WNT pathway-regulated gene expression and other on-target effects of modulating CDK8 and CDK19, including expression of genes regulated by STAT1.?Consistent with this, we find that phosphorylation of STAT1(SER727) is a biomarker of CDK8 kinase activity in vitro and in vivo[1].

In vivo, CCT251545 with WNT-dependent tumors activity[1].

1661839-45-7

C23H24ClN5O

421.92

DMSO:45mg/ml (106.66 Mm)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years