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CGK733 is an inhibitor of kinase ATM and ATR with IC50 value of ~200 nM [1].

Ataxia telangiectasia mutated (ATM) is a serine/threonine kinase which plays pivotal role in DNA repair and cell cycle checkpoints. And when in hypoxia circumstance, loss of ATM-related (ATR) kinase induces the decreasing of HIF-1 DNA binding, which consequently affects GLUT-1 and CAIX expression in the protein level. The components of ATM and ATR regulated signaling pathways which enhances cellular sensitivity to chemo- and radiotherapy thus provide attractive pharmacological targets [2, 3].

CGK733 selectively inhibited ATM and ATR kinase activities and blocked their checkpoint signaling pathways. Treated HEK-293 cells with GSK733 would increase the sensitivity of cells to radiotherapy [1]. When tested with HBV-positive HCC cell line HepG2.2.15, CGK733 treatment significantly increased the cells sensitivity to taxol via inducing the formation of multinucleated cells [2]. Treated with CGK733, senescent breast, lung, and colon carcinoma cells were induced to undergo cell death [4]. CGK733 treated tumor cells could enhance the sensitivity to radio therapy via inhibiting DNA repair and cell cycle checkpoints of tumor cells [5]. In MCF-7 breast cancer cells, CGK733 treatment induced detectable decline levels of cyclin D1 protein and reduced phosphorylated and total retinoblastoma protein (RB) which inhibited cell proliferation [3].

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