CCT244747 is a potent inhibitor of checkpoint kinase 1 (Chk1; IC50 = 8 nM). It is selective for Chk1 over FLT3, Chk2, and CDK1 (IC50s = 600, >10,000, and >10,000 nM, respectively) as well as a panel of 121 additional kinases at a concentration of 10 μM. CCT244747 reverses cell cycle arrest at the G2/M phase induced by etoposide and SN-38 in HT-29 cells and gemcitabine (Item Nos. 11690 | 9003096) in SW620 cells, indicating cellular G2 checkpoint abrogation. It potentiates the genotoxicity of SN-38, gemcitabine, and etoposide in HT-29, SW620, MiaPaCa-2, and Calu-6 cells with potentiation index (PI) values ranging from 1.9-8.5, 2.6-12.2, 5-16, and 1.4-5.6, respectively. In vivo, CCT244747 (75 mg/kg), in combination with irinotecan or gemcitabine, increases the delay of tumor growth in SW620 and Calu-6 mouse xenograft models, respectively.
