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http://dx.doi.org/10.5808/GI.2017.15.4.147

Identification of New Potential APE1 Inhibitors by Pharmacophore Modeling and Molecular Docking  

Lee, In Won (Department of Biological Science, Sangji University)
Yoon, Jonghwan (Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea)
Lee, Gunhee (Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea)
Lee, Minho (Catholic Precision Medicine Research Center, College of Medicine, The Catholic University of Korea)
Publication Information
Genomics & Informatics / v.15, no.4, 2017 , pp. 147-155 More about this Journal
Abstract
Apurinic/apyrimidinic endonuclease 1 (APE1) is an enzyme responsible for the initial step in the base excision repair pathway and is known to be a potential drug target for treating cancers, because its expression is associated with resistance to DNA-damaging anticancer agents. Although several inhibitors already have been identified, the identification of novel kinds of potential inhibitors of APE1 could provide a seed for the development of improved anticancer drugs. For this purpose, we first classified known inhibitors of APE1. According to the classification, we constructed two distinct pharmacophore models. We screened more than 3 million lead-like compounds using the pharmacophores. Hits that fulfilled the features of the pharmacophore models were identified. In addition to the pharmacophore screen, we carried out molecular docking to prioritize hits. Based on these processes, we ultimately identified 1,338 potential inhibitors of APE1 with predicted binding affinities to the enzyme.
Keywords
APE1; molecular docking simulation; pharmacophore modeling; virtual screening;
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