CHIR-124

CHIR-124 is a novel and potent chk1 inhibitor with an IC50 of 0.3 nM. CHIR-124 interacts synergistically with camptothecin in causing growth inhibition in MDA-MB-435 cells as determined by isobologram analysis. In HCT116 human colon carcinoma cells, CHIR-124 increased the effect of SN-38, an active metabolite of irinotecan, in a sequence-dependent manner, with the highest induction of mitotic catastrophe and apoptosis seen when CHIR-124 was given sequentially after SN-38 pretreatment. More importantly, the enhancement of cell death by CHIR-124 was markedly increased in isogenic p53-null and p21-null HCT116 cells.