CCT251545

CCT251545 is an orally bioavailable and potent inhibitor of WNT signaling with an IC₅₀ of 5 nM in 7dF3 cells^[1]. CCT251545 is a selective chemical probe for exploring the role of CDK8 and CDK19 in human disease^[2]. IC50 & Target: IC50: 5 nM (WNT, 7dF3 cells)^[1] In Vitro: CCT251545 potently inhibits WNT pathway activity in COLO205-F1756 clone 4 (an APC -mutant human colorectal cancer cell line engineered to express a modified luciferase-based WNT reporter construct) with an IC₅₀ of 0.035 μM^[1].
CCT251545 has weak inhibition of tankyrase enzymes (TNKS1 IC₅₀ > 10 μM, TNKS2 IC₅₀ = 15.0)^[1].
CCT251545 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^[2].
CCT251545 alters WNT pathway-regulated gene expression and other on-target effects of modulating CDK8 and CDK19, including expression of genes regulated by STAT1^[2].
CCT251545 also reduces phospho-STAT1^SER727 levels in SW620 cells with an IC₅₀ of 9 nM^[2].
CCT251545 displays potent cell-based activity^[2].
In Vivo: CCT251545 (70mg/kg; p.o.; twice daily) causes an inhibition of tumor growth in NCr athymic mice bearing established SW620 human colorectal cancer xenografts^[2].