NU7441 CAS NO.503468-95-9

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 NU7441 increased the cytotoxicity of ionizing radiation and etoposide in SW620, LoVo, and V3-YAC cells but not in V3 cells, confirming that potentiation was due to DNA-PK inhibition. NU7441 substantially retarded the repair of ionizing radiation-induced and etoposide-induced DSB. NU7441 appreciably increased G(2)-M accumulation induced by ionizing radiation, etoposide, and doxorubicin in both SW620 and LoVo cells . NU7441 strongly inhibited DNA-PK in cell lines (IC(50) = 0.3 μM) but only weakly inhibited PI3 K (IC(50) = 7 μM). NU7441 caused doxorubicin- and IR-induced DNA DSBs (measured by γ-H2AX foci) to persist and also slightly decreased homologous recombination activity, as assessed by Rad51 foci [3]. NU7441 is a modest inhibitor of BRD4 and BRDT (IC50 = 1 and 3.5 SM, respectively), which establishes a single hydrogen bond in the KAc site through the chromenone oxygen with Asn140 .