GNE-900 is a an ATP-competitive, selective, and orally active ChK1 inhibitor with IC50s of 0.0011, 1.5 µM for ChKl, ChK2, respectively. GNE-900 abrogates the G2-M checkpoint, enhances DNA damage, and induces Apoptosis. gemcitabine and GNE-900 administration shows anti-tumor activity.
GNE-900 (1 µM; 1-48 h) induces apoptosis with increases in the expression of cleaved PARP when combined with gemcitabine (50 nM) in HT-29 cells[1].
GNE-900 (2.5-40 mg/kg; p.o.; once) decreases the tumor volume and increases DNA damage, γ-H2AX levels when combinated with gemcitabine in rats[1].
References:
[1]. Blackwood E, et al. Combination drug scheduling defines a window of opportunity for chemopotentiation of gemcitabine by an orally bioavailable, selective ChK1 inhibitor, GNE-900. Mol Cancer Ther. 2013 Oct;12(10):1968-80.