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Bioorg Med Chem. 2017 May 1;25(9):2531-2544. doi: 10.1016/j.bmc.2017.01.028. Epub 2017 Jan 21.

Inhibitors of nuclease and redox activity of apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1).

Author information

1
Vorozhtsov Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences, pr. akademika Lavrent'eva 9, Novosibirsk 630090, Russian Federation. Electronic address: sergey@nioch.nsc.ru.
2
Vorozhtsov Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences, pr. akademika Lavrent'eva 9, Novosibirsk 630090, Russian Federation; Novosibirsk State University, Pirogova Str. 2, Novosibirsk 630090, Russian Federation.
3
Novosibirsk State University, Pirogova Str. 2, Novosibirsk 630090, Russian Federation; Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Division, Russian Academy of Sciences, pr. akademika Lavrent'eva 8, Novosibirsk 630090, Russian Federation.

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 APE1/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 APE1/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.

KEYWORDS:

Apurinic/apyrimidinic (AP) site; Apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1); Base excision repair (BER); DNA repair; E3330; Inhibitors; Lucanthone; Methoxyamine

PMID:
28161249
DOI:
10.1016/j.bmc.2017.01.028
[Indexed for MEDLINE]

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