Developments of DNA-dependent Protein Kinase Inhibitors as Anticancer Agents

Repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genome integrity, cell survival, and prevention tumorigenesis. Three pathways are responsible for the repair of DNA DSBs: homologous recombination (HR), single strand annealing (SSA) and non-homologous end joining (NHEJ). DNA-dependent Protein Kinase (DNAPK), the key component of the NHEJ pathway, becomes an important target for cancer therapy. A large number of small molecules exhibit inhibitory activities against DNA-PK in an ATP-competitive manner. This paper reviews the recent developments of a diversity of small molecule DNA-PK inhibitors, with emphasis on their structural features, biological activities, and structure-activity relationships (SARs).