Wei Zhang, Lu Zhou, Zihao Li
Nov 23, 2012
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Journal
Medicinal Chemistry Research
Abstract
Many researches discover that 3-phosphoinositide-dependent protein kinase-1 (PDK1) is overexpressed in many cancer cells and a promising target for developing novel anticancer drugs. The aim of this study is to identify novel scaffolds and utilize them in designing potent PDK1 inhibitors. 3D pharmacophore models were established based on the known PDK1 inhibitors. The best pharmacophore model, Hypo1, was selected, validated, and used in virtual screening. The obtained compounds were subjected to Lipinski’s rule of five, ADMET filtrations, and molecular docking studies. Finally, five molecules with high Genetic Optimization for Ligand Docking fitness scores and interactions with critical active site amino acids were identified. These hit compounds may act as novel leads for PDK1 inhibitors design.