Virtual screening for Raf-1 kinase inhibitors based on pharmacophore model of substituted ureas
Date
2009
Authors
Li, H.F.
Lu, T.
Zhu, T.
Jiang, Y.J.
Rao, S.S.
Hu, L.Y.
Xin, B.T.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
European Journal of Medicinal Chemistry, 2009; 44(3):1240-1249
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Abstract
A three-dimensional (3D) quantitative pharmacophore model was developed from a training set of structurally diverse substituted ureas against Raf-1 kinase, which was well validated to be highly predictive by two methods, namely, test set prediction and Cat-Scramble method. Then a virtual database searching was performed with the pharmacophore model as a 3D query, and the bioactivities of the retrieved hits were predicted by the pharmacophore. Subsequently, molecular docking was carried out on the selected hits whose estimated IC50 was less than 1 μM. Finally, 29 hits were identified as potential leads against Raf-1 kinase, which exhibited good estimated activities, high docking scores, similar binding mode to experimentally proven compounds and favorable drug-like properties. The study may facilitate the discovery and rational design of novel leads with potent inhibitory activity targeting Raf-1 kinase.
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Dissertation Note
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Description
Data source: Figures & tables, https://doi.org/10.1016/j.ejmech.2008.09.016
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Copyright 2008 Elsevier Masson SAS