NSC 109555

Description

NSC 109555 is an ATP-competitive inhibitor of checkpoint kinase 2 Chk2; IC50=200 nM in a cell-free kinase assay . It is selective for Chk2 over Chk1 and 16 kinases in a panel but does inhibit Brk, c-Met, IGFR, and LCK with IC50 values of 210, 6,000, 7,400, and 7,100 nM, respectively. NSC 109555 inhibits Chk2 autophosphorylation and phosphorylation of the Chk2 substrate histone H1 in vitro IC50=240 nM . It inhibits the growth of, and induces autophagy in, L1210 leukemia cells in vitro.2 NSC 109555 1,250 nM potentiates gemcitabine-induced cytotoxicity in MIA PaCa-2, CFPAC-1, PANC-1, and BxPC-3 pancreatic cancer cells, as well as reduces gemcitabine-induced increases in Chk2 phosphorylation and enhances gemcitabine-induced production of reactive oxygen species ROS in MIA PaCa-2 cells.