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

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19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2531-2544
Number of pages14
JournalBioorganic and Medicinal Chemistry
Volume25
Issue number9
DOIs
Publication statusPublished - 1 May 2017

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
  • BASE-EXCISION-REPAIR
  • APURINIC-APYRIMIDINIC ENDONUCLEASE
  • FACTOR-I
  • SIGNALING PROTEIN APE1/REF-1
  • ABASIC ENDONUCLEASE
  • SMALL-MOLECULE INHIBITOR
  • DNA-BINDING ACTIVITY
  • CELL LUNG-CANCER
  • HUMAN AP ENDONUCLEASE-1
  • NF-KAPPA-B
  • Humans
  • DNA Repair/drug effects
  • Enzyme Inhibitors/chemistry
  • Oxidation-Reduction
  • Neoplasms/drug therapy
  • DNA-(Apurinic or Apyrimidinic Site) Lyase/antagonists & inhibitors
  • Antineoplastic Agents/chemistry
  • Animals
  • Cell Line, Tumor

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