KU-55933

Potent and selective ATM kinase inhibitor IC50s= 13, 2500, 9300, 16600, >100000 and >100000 nM for ATM, DNA-PK, mTOR, PI 3-kinase, PI 4-K and ATR respectively [1]. Decreases viability of MCF-7, A549 and HCT116 cells and decreases p21CIP1 levels in vitro [2]. Disruption of ATM signaling in primary A-T fibroblasts leads to dysregulation of ribonucleotide reductase and increase resistance to inhibitors of mitochondrial respiration and translation [3]. Sensitizes radio-resistant cancer cells [4]. Provides neuroprotection against H2O2-induced cell damage [5].

References:

1) Hickson et al. (2004), Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM;  Cancer Res., 64 9152

2) Crescenzi et al. (2008), Ataxia telangiectasia mutated and p21CIP1 modulate cell survival of drug-induced senescent tumor cells: implications for chemotherapy;  Clin. Cancer Res. 14 1877

3) Eaton et al. (2007), Ataxia-telangiectasia mutated kinase regulates ribonucleotide reductase and mitochondrial homeostasis;  J. Clin. Invest., 117 2723

4) T Zhang et al. (2015) The ATM inhibitor KU55933 sensitizes radioresistant bladder cancer cells with DAB2IP gene defect;  Int. J. Radiat. Biol., 91:368

5) J Chwastek et al. (2017) The ATM kinase inhibitor KU-55933 provides neuroprotection against hydrogen peroxide-induced cell damage via a yH2AX/p-p53/caspase-3-independent mechanism: Inhibition of calpain and cathepsin D;  Int. J. Biochem. Cell Biol. 87:38