Pharmacophore Identification of Hydroxamate HDAC 1 Inhibitors
Liqin YU
Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 210009, China
Search for more papers by this authorFei LIU
Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 210009, China
Search for more papers by this authorYadong CHEN
Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 210009, China
Search for more papers by this authorLiqin YU
Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 210009, China
Search for more papers by this authorFei LIU
Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 210009, China
Search for more papers by this authorYadong CHEN
Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 210009, China
Search for more papers by this authorAbstract
A three-dimensional pharmacophore model was established based on 24 hydroxamate histone deacetylase (HDAC) inhibitors by HypoGen algorithm embedded in Catalyst software. The best pharmacophore hypothesis (Hypo1), consisting of four chemical features (one hydrogen-bond acceptor, one aromatic ring and two hydrophobic groups), has a correlation coefficient of 0.946. The Hypol was also validated by a test set consisting of 20 other compounds. Compared with the prior studies towards HDAC inhibitors the detailed chemical features of the "CAP" region in the reported HDAC inhibitors were for the first time depicted, which would be helpful in the further designing of novel HDAC inhibitors.
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