Discovery of novel focal adhesion kinase inhibitors using a hybrid protocol of virtual screening approach based on multicomplex-based pharmacophore and molecular docking

• Published in: International journal of molecular sciences Vol. 13; no. 12; pp. 15668 - 15678
• Main Authors: Wu, Fengbo, Xu, Ting, He, Gu, Ouyang, Liang, Han, Bo, Peng, Cheng, Song, Xiangrong, Xiang, Mingli
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23-11-2012; Molecular Diversity Preservation International (MDPI)
• Subjects: Cancer; Chinese medicine; Drug Discovery; Drug Evaluation, Preclinical; focal adhesion kinase; Focal Adhesion Kinase 1 - antagonists & inhibitors; Focal Adhesion Kinase 1 - chemistry; Humans; Hydrogen bonds; Kinases; Ligands; molecular docking; Molecular Docking Simulation; pharmacophore; Phosphorylation; Protein Kinase Inhibitors - chemistry; Tumors; virtual screening; China
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms131215668

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.