CHIR-124

CHIR-124 is a potent, selective, quinolone-based small molecule inhibitor of checkpoint kinase 1 (Chk1), with an IC50 of 0.3 nM in cell-free assays. It demonstrates over 2,000-fold selectivity for Chk1 versus Chk2 and has been shown to abrogate S and G2-M phase cell cycle checkpoints in response to DNA damage. By inhibiting Chk1, CHIR-124 potentiates the cytotoxicity of topoisomerase I poisons (such as camptothecin or SN-38) and enhances apoptosis in p53-deficient tumor cells. Preclinical studies indicate promising antitumor activity when used in combination with DNA-damaging agents or mTOR inhibitors, particularly in MYC-driven cancers. The drug is experimental and has not advanced beyond preclinical or early clinical development[1][2][3][4][5][8].