CHIR-124

CHIR-124 is a potent, selective Chk1 inhibitor with in vitro IC50 of 0.3 nM, 2,000-fold selectivity over Chk2; displays 500- to 5,000-fold less active against other cell cycle kinases, such as CDK2/cyclin A , Cdc2/cyclin B, and CDK4/cyclin D; also potently inhibits PDGFR and FLT3 with IC50s of 6.6 nM and 5.8 nM; interacts synergistically with topoisomerase poisons (e.g., camptothecin or SN-38) in causing growth inhibition in several p53-mutant solid tumor cell lines, abrogates the SN-38-induced S and G2-M checkpoints and potentiates apoptosis in MDA-MD-435 breast cancer cells, also restores the level of cdc25A protein; potentiates the growth inhibitory effects of irinotecan in breast cancer xenograft models.