Combined pharmacophore modeling, 3D-QSAR and docking studies to identify novel HDAC inhibitors using drug repurposing |
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| Authors: | Jian Liu Yehua Zhu Yufang He Haohao Zhu Yi Gao Zhi Li |
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| Institution: | 1. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China;2. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing, Jiangsu, China;3. Jiangsu Key Laboratory for Functional Substances of Chinese Medicine Stake Key Laboratory Cultivation Base for TCM Quality and Efficacy School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China |
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| Abstract: | AbstractHistone deacetylases (HDACs), a critical family of epigenetic enzymes, has emerged as a promising target for antitumor drugs. Here, we describe our protocol of virtual screening in identification of novel potential HDAC inhibitors through pharmacophore modeling, 3D-QSAR, molecular docking and molecular dynamics (MD) simulation. Considering the limitation of current virtual screening works, drug repurposing strategy was applied to discover druggable HDAC inhibitor. The ligand-based pharmacophore and 3D-QSAR models were established, and their reliability was validated by different methods. Then, the DrugBank database was screened, followed by molecular docking. MD simulation (100?ns) was performed to further study the stability of ligand binding modes. Finally, results indicated the hit DB03889 with high in silico inhibitory potency was suitable for further experimental analysis.Communicated by Ramaswamy H. Sarma |
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| Keywords: | HDAC inhibitors virtual screening drug repurposing 3D-QSAR pharmacophore |
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