GNE-900 (GNE900) is a potent, selective, ATP-competitive, and orally bioavailable Chk1 inhibitor with IC50 of <1 nM.
GNE-900 displays >300-fold selectivity over Aurora, PLK, CDK1/2) and ChK2.
GNE-900 abrogates DNA damage-induced S and G2–M checkpoints (EC50=61.8 nM in H-29 cells), and exacerbates DNA double-strand breaks (DSB) to induce cell death, accelerates the demise of damaged HCT-116 colorectal cancer cells in a p53-dependent manner in vitro.
GNE-900 potentiates the efficacy of gemcitabine in tumor xenografts.
