NSC 109555

NSC 109555 is an ATP-competitive inhibitor of checkpoint kinase 2 (Chk2; IC₅₀ = 200 nM in a cell-free kinase assay).¹ 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.³

WARNING This product is not for human or veterinary use.

1. Jobson, A.G., Cardellina, J.H., II, Scudiero, D., et al. Identification of a bis-guanylhydrazone [4,4'-diacetyldiphenylurea-bis(guanylhydrazone); NSC 109555] as a novel chemotype for inhibition of Chk2 kinase. Mol. Pharm. 72(4), 876-884 (2007).

2. Mikles-Robertson, F., Dave, C., and Porter, C.W. Apparent autophagocytosis of mitochondria in L1210 leukemia cells treated in vitro with 4,4'-diacetyl-diphenylurea-bis(guanylhydrazone). Cancer Res. 40(4), 1054-1061 (1980).

3. Duong, H.-Q., Hong, Y.B., Kim, J.S., et al. Inhibition of checkpoint kinase 2 (CHK2) enhances sensitivity of pancreatic adenocarcinoma cells to gemcitabine. J. Cell. Mol. Med. 17(10), 1261-1270 (2013).