CCT-251921

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

一种有效的、选择性的、口服生物可利用的 CDK8 和 CDK19 抑制剂，IC50 分别为 2.3 nM 和 2.6 nM。

A potent, selective, and orally bioavailable inhibitor of CDK8 and CDK19 with IC50of 2.3 nM and 2.6 nM respectively; reduces STAT1 Ser727 phosphorylation, inhibits tunor growth of APC-mutant SW620 human colorectal carcinoma xenograft mode, has pharmacokinetic, and physicochemical properties.

CCT-251921 has acceptable aqueous solubility and demonstrates minimal activity when tested in a panel of 55 receptors, ion channels, and enzymes at 1 μM and in a panel of 279 kinases; weak inhibition of CYPs is observed. CCT-251921 demonstrates potent inhibition of reporter-based readouts measuring basal WNT pathway activity in human cancer cell lines that have constitutively activated WNT pathway signaling: LS174T (β-catenin mutant), SW480 and Colo205 (APC mutant) or PA-1 human teratocarcinoma cells that are WNT ligand dependent.

CCT-251921 shows improved oral pharmacokinetics and pharmaceutical properties in order to facilitate further evaluation of CDK8/19 pharmacology and progression into preclinical efficacy and safety studies.In APC-mutant SW620 human colorectal carcinoma xenograft model, CCT-251921 treatment reduces mice tumor weight (54.2%) at day 15.The inhibition of STAT1SER727 phosphorylation is maintained for more than 6 h after the last dose.

CCT 251921 | CCT251921

Angiogenesis

CDK

CDK

Cancer

——

1607837-31-9

410.906

C21H23ClN6O

>98% (HPLC)

DMSO : ≥ 28 mg/mL. 68.14 mM

O=C1NCCC12CCN(C3=C(Cl)C(N)=NC=C3C4=CC5=C(N(C)N=C5)C=C4)CC2

8-(2-Amino-3-chloro-5-(1-methyl-1H-indazol-5-yl)pyridin-4-yl)-2,8-diazaspiro[4.5]decan-1-one

(-20℃)

With Ice Pack

≥ 2 years