title: Discovery of novel focal adhesion kinase inhibitors using a hybrid protocol of virtual screening approach based on multicomplex-based pharmacophore and molecular docking.
abstract: Focal adhesion kinase (FAK) is a tyrosine kinase that functions as a key orchestrator of signals leading to invasion and metastasis. In the current study, the multicomplex-based pharmacophore (MCBP)-guided method has been suggested to generate a comprehensive pharmacophore of FAK kinase based on seven crystal structures of FAK-inhibitor complexes. In this investigation, a hybrid protocol of virtual screening methods, comprising of pharmacophore model-based virtual screening (PB-VS) and docking-based virtual screening (DB-VS), is used for retrieving new FAK inhibitors from commercially available chemical databases. This hybrid virtual screening approach was then applied to screen several chemical databases, including the Specs (202,408 compounds) database. Thirty-five compounds were selected from the final hits and should be shifted to experimental studies. These results may provide important information for further research of novel FAK inhibitors.
authors: Department of Pharmacy and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. hegu@scu.edu.cn.
authors: Fengbo
authors: F
authors: Wu
authors: Ting
authors: T
authors: Xu
authors: Gu
authors: G
authors: He
authors: Liang
authors: L
authors: Ouyang
authors: Bo
authors: B
authors: Han
authors: Cheng
authors: C
authors: Peng
authors: Xiangrong
authors: X
authors: Song
authors: Mingli
authors: M
authors: Xiang
mesh_terms: D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D006801:Humans; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000737:chemistry*
chemical_list: D047428:Protein Kinase Inhibitors; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human