alexa Inhibition of the DNA-Dependent Protein Kinase for Cancer Therapy
ISSN: 2161-0444

Medicinal Chemistry
Open Access

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Research Article

Inhibition of the DNA-Dependent Protein Kinase for Cancer Therapy

Suzannah J Harnor, Alfie Brennan and Céline Cano*

Northern Institute for Cancer Research, School of Chemistry, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK

*Corresponding Author:
Céline Cano
Northern Institute for Cancer Research, School of Chemistry
Newcastle University, Bedson Building, Newcastle upon Tyne, NE1 7RU, UK
Tel: 4401912087060
E-mail: [email protected]

Received date: May 22, 2017; Accepted date: May 27, 2017; Published date: June 03, 2017

Citation: Harnor SJ, Brennan A, Cano C (2017) Inhibition of the DNA-Dependent Protein Kinase for Cancer Therapy. Med Chem (Los Angeles) 7: 172-177. doi:10.4172/2161-0444.1000452

Copyright: © 2017 Harnor SJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

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The catalytic activity of DNA-dependent protein kinase (DNA-PK) is central to its ability to repair lethal DNAdouble strand breaks (DSBs). This includes repair of DSB lesions following therapeutic treatment of cancer cells or resulting from oxidative stress or oncogene-induced transcription. As a tactic to induce tumour chemo- and radio-sensitisation, numerous attempts have been made to identify small molecule inhibitors of DNA-PK activity. This review examines the structures of known reversible and irreversible inhibitors, including those based upon chromen-4-one, arylmorpholine, and benzaldehyde scaffolds. VX-984 and M3814 are recent examples of DNA-PK catalytic inhibitors that have progressed into clinical development, the results from which should help to further advance our understanding of whether this approach represents a promising therapeutic strategy for the treatment of cancer.

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