Developments of DNA-dependent Protein Kinase Inhibitors as Anticancer Agents

Title:Developments of DNA-dependent Protein Kinase Inhibitors as Anticancer Agents

Volume: 14 Issue: 11

Author(s): Chen-Chen Ma, Hui Li, Ren-Zhong Wan and Zhao-Peng Liu

Affiliation:

Keywords: Anticancer, anticancer agents, ATP-competitive inhibitors, chemo- and radio-potentiation, DNA-dependent protein kinase (DNA-PK), DNA double-strand breaks (DSBs), DNA-PK inhibitors, DNA-PK catalytic subunit, PI3K, cytotoxicity, inhibitory activity, kinase selectivity.

Abstract: 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).

Cite this article as:

Ma Chen-Chen, Li Hui, Wan Ren-Zhong and Liu Zhao-Peng, Developments of DNA-dependent Protein Kinase Inhibitors as Anticancer Agents, Mini-Reviews in Medicinal Chemistry 2014; 14 (11) . https://dx.doi.org/10.2174/1389557514666141013141924