Cellular and Molecular Life Sciences

, Volume 67, Issue 21, pp 3621–3631

Small molecule inhibitors of DNA repair nuclease activities of APE1

Multi-Author Review


APE1 is a multifunctional protein that possesses several nuclease activities, including the ability to incise at apurinic/apyrimidinic (AP) sites in DNA or RNA, to excise 3′-blocking termini from DNA ends, and to cleave at certain oxidized base lesions in DNA. Pre-clinical and clinical data indicate a role for APE1 in the pathogenesis of cancer and in resistance to DNA-interactive drugs, particularly monofunctional alkylators and antimetabolites. In an effort to improve the efficacy of therapeutic compounds, such as temozolomide, groups have begun to develop high-throughput screening assays and to identify small molecule inhibitors against APE1 repair nuclease activities. It is envisioned that such inhibitors will be used in combinatorial treatment paradigms to enhance the efficacy of DNA-interactive drugs that introduce relevant cytotoxic DNA lesions. In this review, we summarize the current state of the efforts to design potent and selective inhibitors against APE1 AP site incision activity.


APE1/APEX1/REF-1 Abasic endonuclease DNA damage Base excision DNA repair Inhibitor Cancer treatment 

Copyright information

© US Government 2010

Authors and Affiliations

  1. 1.Laboratory of Molecular Gerontology, Biomedical Research CenterNational Institute on Aging, NIH, IRPBaltimoreUSA
  2. 2.NIH Chemical Genomics Center, National Human Genome Research InstituteNational Institutes of HealthBethesdaUSA

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