An orally bioavailable ATP-competitive inhibitor of DNA-dependent protein kinase (DNA-PK), with potential chemo/radiosensitizing and antineoplastic activites. Upon oral administration, DNA-PK inhibitor AZD7648 selectively targets, binds to and inhibits the activity of DNA-PK, thereby interfering with the non-homologous end joining (NHEJ) process and preventing repair of DNA double strand breaks (DSBs) caused by ionizing radiation or chemotherapeutic treatment. This increases chemo- and radiotherapy cytotoxicity leading to enhanced tumor cell death. AZD7648 may also increase the effect of poly(ADP-ribose) polymerase (PARP) inhibitors and may work as a monotherapy in tumors with high endogenous levels of DNA damage resulting from defects in other DNA repair pathways. The enhanced ability of tumor cells to repair DSBs plays a major role in the resistance of tumor cells to chemo- and radiotherapy. DNA-PK plays a key role in the NHEJ pathway and DSB repair.