CCT245737 is a orally active and seletive Chk1 inhibitor, with an IC50 of 1.3 nM.
CAS：1489389-18-5
分子式：C16H16F3N7O
分子量：379.34
纯度：98%
存储：Store at -20°C

Background:

CCT245737 is a orally active and seletive Chk1 inhibitor, with an IC50 of 1.3 nM.

CCT245737 (10 uM) shows >80% inhibition of a panel of 124 kinases, including ERK8, PKD1, RSK2 and RSK1 with IC50s of 130, 298, 361 and 362 nM[1]. CCT245737 abrogates an etoposide-induced G2 checkpoint in HT29, SW620, MiaPaCa-2, and Calu6 cell lines, with IC50s ranging from 30 to 220 nM[2].

CCT245737 (150 mg/kg p.o.) inhibits tumor growth in combination with gemcitabine (100 mg/kg iv) in HT29 colon cancer xenografts. CCT245737 (300 mg/kg, p.o.) also inhibits the gemcitabine (60 mg/kg iv) induced pSer296 CHK1 autophosphorylation at 24 h in SW620 human colon cancer xenografts[1]. CCT245737 (150 mg/kg, p.o) alone significantly inhibits tumor growth in an Eu-Myc mouse model of human B-cell lymphocytic leukemia[2].

参考文献:
[1]. Osborne JD, 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, 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.