CCT251545 is an orally bioavailable and potent inhibitor of WNT signaling with an IC50 of 5 nM in 7dF3 cells. CCT251545 is a selective chemical probe for exploring the role of CDK8 and CDK19 in human disease.
IC50&Target
IC50: 5 nM (WNT, 7dF3 cells)
体外研究
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.
CCT251545 has weak inhibition of tankyrase enzymes (TNKS1 IC50 > 10 μM, TNKS2 IC50 = 15.0).
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.
CCT251545 alters WNT pathway-regulated gene expression and other on-target effects of modulating CDK8 and CDK19, including expression of genes regulated by STAT1.
CCT251545 also reduces phospho-STAT1 levels in SW620 cells with an IC50 of 9 nM.
CCT251545 displays potent cell-based activity.
体内研究
CCT251545 (70mg/kg; p.o.; twice daily) causes an inhibition of tumor growth in NCr athymic mice bearing established SW620 human colorectal cancer xenografts.
Animal Model:
6-8 weeks female NCr athymic mice bearing established SW620 xenografts
Dosage:
70mg/kg
Administration:
Oral administration; twice daily; from days 0-7 and days 10-14
Result:
Caused an inhibition of tumor growth with a 70% reduction in final tumor weight relative to control.
分子式
C23H24ClN5O
分子量
421.92
CAS号
1661839-45-7
运输条件
Room temperature in continental US; may vary elsewhere.