Inhibitors of nuclease and redox activity of apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1).
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.
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.
Sergey S
SS
Laev
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.
Nariman F
NF
Salakhutdinov
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.
Olga I
OI
Lavrik
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004260:DNA Repair / Q000187:drug effects; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D010084:Oxidation-Reduction
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
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