Regular p53 WT individual fibroblasts showed no radiosensitization with AZD7762. Two H460 cell lines Crizotinib structure were compared that differed only within their p53 status, to further test the dependence of AZD7762 mediated radiation sensitization on p53 status. As shown in Fig. D, AZD7762 and 1c radiosensitized H460 DN p53 cells to a better extent than H460 WT cells. The radiosensitivity of two human pancreatic and one glioblastoma cell lines was also enhanced by AZD7762. Most of the studies described above used exponentially growing cell cultures. When confluent cultures of HT29 cells were employed no radiosensitization by AZD7762 was observed. When compared with exponentially growing HT29 cells, the plateau phase HT29 cells were enriched in the G1 cell cycle phase. Hence, active movement through Cellular differentiation the cell cycle is essential for maximum AZD7762 radiation sensitization. AZD7762 Abrogates Radiation Induced G2 Arrest Chk1 inhibition is demonstrated to result in an abrogation of the G2 checkpoint subsequent treatment with DNA damaging cytotoxic drugs. To determine if AZD7762 may equally abrogate radiation-induced G2 arrest, circulation cytometry studies were performed for irradiated cells treated with or without AZD7762. A series of flow profiles were generated for all cell lines as a function of time after treatment and the results of AZD7762 treatment around the radiation-induced G2 arrest are summarized in Fig. 2 and Supplementary Fig. S6A, B. Regardless of the p53 status, all cell lines evaluated demonstrated a G2 arrest following radiation therapy. Likewise, AZD7762 abrogated rays induced G2 arrest for many cell lines. Hence, there was no relationship between abrogation of the G2 arrest and AZD7762 mediated radiation sensitization. AZD7762 Ibrutinib 936563-96-1 Inhibits Radiation Induced DNA Damage Repair and Enhances Radiation Induced Mitotic Catastrophe To determine the influence of AZD7762 on radiation induced immediate DNA damage and DNA damage repair, phosphorylated H2AX induction and mitotic catastrophe were considered respectively. Fig. 3A and B and Supplementary Fig. S7A and B show the results of AZD7762 on radiation induced H2AX induction for four cell lines. In response to radiation alone, phosphorylated H2AX amounts rapidly increased following radiation, but with time returned to near control values by 24 hr indicating the repair of DNA double strand breaks. For HT29, DU145, and A549 cells AZD7762 inhibited repair at 8 and 24 hr post light most abundant in inhibition noted in HT29 and DU145 cells, a tiny amount repair inhibition in A549 cells and almost no inhibition noticed for 1522 cells. AZD7762 enhanced the radiosensitivity of numerous cancer cell lines. AZD7762 cytotoxicity alone was minimal for several cell lines studied. Lastly, AZD7762 therapy alone or in combination with radiation triggered no accumulation.