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CAS No.: 1489389-18-5

CCT245737 Catalog No. CSN18829

Synonyms: SRA737

CCT245737 is a potent, ATP-competitive CHK1 inhibitor with an IC50 of 30-220 nM.

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生物活性

实验方案

技术信息

生物活性

描述CCT245737 is the first orally active, clinical development candidate and highly selective CHK1 inhibitor with IC50 value of 1.4nM. CCT245737 could potentiate the cytotoxicity of several genotoxic drugs in multiple human tumor cell lines and human tumor xenograft models. CCT245737 at concentration of 0.5, 1, 2 and 5μM led a marked loss of pS296 and pS317 (but not S280 or S345) of CHK1 induced by gemcitabine in HT29 colon cancer cells. An apparent decrease in the G1/Go population and a concomitant increase in the S' population, as well as abrogated an etoposide-induced G2/M arrest in HT29 cells could also be observed at concentration>0.5μM post 24h. These suggested the CHK1 inhibition by CCT245737 abrogated gemcitabine induced cell cycle arrest causing DNA damage and cell death. A single dose of CCT245737 (50 or 100mg/kg p.o.) led to the in vivo CHK1 inhibition shown by decreased pS296 and pS317 (combined with gemcitabine at 100mg/kg) post 24h. Combined treatment of CCT245737 at 150mg/kg (p.o.) enhanced the antitumor effects of gemcitabine (100mg/kg i.v.) in HT29 human colon cancer xenografts. Similar potentiation of antitumor effects of irinotecan in HT29 human colon carcinoma xenografts or gemcitabine in SW620 human colon cancer xenografts could also be achieved by administration of CCT245737.
作用机制CCT245737 binds in the ATP pocket of human CHK1. It is an ATP competitive inhibitor.
参考文献

[1] Osborne JD, Matthews TP, et al. Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737). J Med Chem. 2016 Jun 9;59(11):5221-37.
[2] Walton MI, Eve PD, et al. The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eµ-MYC driven B-cell lymphoma. Oncotarget. 2016 Jan 19;7(3):2329-42.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.6362 mL
- 13.1808 mL
- 26.3616 mL
- 5 mM
- 0.5272 mL
- 2.6362 mL
- 5.2723 mL
- 10 mM
- 0.2636 mL
- 1.3181 mL
- 2.6362 mL

技术信息

CAS号

1489389-18-5

储存条件

粉末: Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C16H16F3N7O

运输

蓝冰

分子量

379.34

别名

SRA737

溶解度

DMSO	22.86 mg/mL (60.3 mM)
Water	insoluble

动物实验配方

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