CCT245737

CCT245737 (SRA737) is an orally active and seletive Chk1 inhibitor, with an IC₅₀ of 1.3 nM. IC50 & Target:IC50: 1.3 nM (Chk1), 2440 nM (Chk2)^[1] In Vitro: CCT245737 (10 µM) 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 VP-16-induced G2 checkpoint in HT29, SW620, MiaPaCa-2, and Calu6 cell lines, with IC₅₀s ranging from 30 to 220 nM^[2]. In Vivo: CCT245737 (150 mg/kg p.o.) inhibits tumor growth in combination with LY 188011 (100 mg/kg iv) in HT29 colon cancer xenografts. CCT245737 (300 mg/kg, p.o.) also inhibits the LY 188011 (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 Eμ-Myc mouse model of human B-cell lymphocytic leukemia^[2].