Abstract: Human apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multifunctional protein which is essential in the base excision repair (BER) pathway of DNA lesions caused by oxidation and alkylation. This protein hydrolyzes DNA adjacent to the 5'-end of an apurinic/apyrimidinic (AP) site to produce a nick with a 3'-hydroxyl group and a 5'-deoxyribose phosphate moiety or activates the DNA binding activity of certain transcription factors through its redox function. Studies have indicated a role for APEl/Ref-1 in the pathogenesis of cancer and in resistance to DNA-interactive drugs. Thus, this protein has potential as a target in cancer treatment. As a result, major efforts have been directed to identify small molecule inhibitors against APEl/Ref-1 activities. These agents have the potential to become anticancer drugs. The aim of this review is to present recent progress in studies of all published small molecule APE1/Ref-1 inhibitors. The structures and activities of APE1/Ref-1 inhibitors, that target both DNA repair and redox activities, are presented and discussed. To date, there is an urgent need for further development of the design and synthesis of APE1/Ref-1 inhibitors due to high importance of this protein target. (C) 2017 Elsevier Ltd. All rights reserved.

Cite: Laev S.S. , Salakhutdinov N.F. , Lavrik O.I.
Inhibitors of nuclease and redox activity of apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1)
Bioorganic and Medicinal Chemistry. 2017. V.25. N9. P.2531-2544. DOI: 10.1016/j.bmc.2017.01.028 WOS Scopus РИНЦ

Dates:

Published print:

May 1, 2017

Identifiers:

Web of science	WOS:000399437200001
Scopus	2-s2.0-85011068071
Elibrary	29477741
OpenAlex	W2577709858

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