In vitro
AZD7762 is a inhibitor of checkpoint kinase 1 (Chk1), which functions as a regulatory kinase in cell cycle progression and is a critical effector of the DNA-damage response. As a ATP competitive inhibitor, AZD7762 binds in the ATP-binding site of Chk1 and inhibit Chk1 phosphorylation of a cdc25C peptide with an IC 50 of 5 nM. AZD7762 abrogated checkpoint cell cycle arrest mediated by DNA-Damaging agents. AZD7762 was shown to abrogate the G 2 arrest induced by camptothecin with an average EC 50 of 10 nM and maximal abrogation in the range of 100 nM. AZD7762 treatment enhanced the radiosensitivity of p53-mutated tumor cell lines to a greater extent than for p53 wild-type tumor lines. AZD7762 treatment abrogated radiation-induced G(2) delay, inhibited radiation damage repair (assessed by gamma-H2AX), and suppressed radiation-induced cyclin B expression.
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