Ataxia-telangiectasia mutated (ATM) is a serine/threonine kinase that activates checkpoint signaling following double strand DNA breaks and genotoxic stress. Ku-60019 is a potent, reversible inhibitor of ATM kinase (IC50 = 6.3 nM), blocking the phosphorylation of ATM substrate proteins. It is much less effective or without effect against a panel of 229 other kinases. Ku-60019 sensitizes glioma cells to radiation and inhibits migration and invasion of glioma cells in vitro. It produces radiosensitization and increases survival in vivo when administered intra-tumorally in orthotopic xenograft models of glioblastoma multiforme. Ku-60019 is particularly effective in producing lethality in cells with mutant p53 or that are deficient in PTEN.
