CCT251545

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

CCT251545 是一种有效的、口服生物可利用的 Wnt 信号传导抑制剂，IC50 为 5 nM，也是一种有效的 CDK8 和 CDK19 选择性化学探针，其选择性比 291 种其他激酶高 100 倍；在缺乏 WNT 配体的情况下，有效抑制 LS174T 和 SW480 细胞中基于报告基因的基础 WNT 通路活性读数，IC50 分别为 23 和 190 nM。

CCT251545 is a potent, orally bioavailable inhibitor of Wnt signaling with IC50 of 5 nM, also is a potent and selective chemical probe for CDK8 and CDK19 with >100-fold selectivity over 291 other kinases; potently inhibits reporter-based readouts of basal WNT pathway activity in LS174T and SW480 cells in the absence of WNT ligand with IC50 of 23 and 190 nM, respectively; demonstrates potent inhibition of WNT pathway activity in APC mutant human colorectal cancer cell line with IC50 of 35 nM; inhibits phospho-STAT1SER727 levels in SW620 cells with IC50 of 9 nM; demonstrate in vivo activity in WNT-dependent tumors.

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-STAT1SER727 levels in SW620 cells with an IC50 of 9 nM.CCT251545 displays potent cell-based activity.

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 10-14Result:Caused an inhibition of tumor growth with a 70% reduction in final tumor weight relative to control.

CCT 251545 | CCT-251545

Angiogenesis

CDK

CDK

Cancer

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1661839-45-7

421.9225

C23H24ClN5O

>98% (HPLC)

DMSO: ≥ 50 mg/mL

O=C1NCCC12CCN(C3=C(Cl)C=NC=C3C4=CC=C(C5=CN(C)N=C5)C=C4)CC2

2,8-Diazaspiro[4.5]decan-1-one, 8-[3-chloro-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]-4-pyridinyl]-

(-20℃)

With Ice Pack

≥ 2 years