title: Recent advances in structure-based drug design and virtual screening of VEGFR tyrosine kinase inhibitors.
abstract: During the past decade, developments in computational processing and X-ray crystallography have allowed virtual screening become integrated into drug discovery campaigns. This review focuses on the recent advancements in the drug discovery of VEGFR2 tyrosine kinase inhibitors (VEGFR2 TKIs) by using in silico methodologies. An introduction for the methodology framework of pharmacophore modeling, molecular docking and structure-based design are provided. We discuss the recent studies on the structures of VEGFR2 protein kinase in different binding modes, and the insights on molecular interactions gained from knowledge of the co-crystal structures complex with structurally diverse VEGFR2 inhibitors. We provide some aspects of model construction and molecular docking techniques. Several representative examples of successful applications on VEGFR2 virtual screening for hit discovery, lead optimization and structure-based design are also presented.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao, China. Electronic address: maghoi@umac.mo.
authors.forename: Pui Man
authors.initials: PM
authors.lastname: Hoi
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao, China.
authors.forename: Shang
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao, China.
authors.forename: Chi Teng
authors.initials: CT
authors.lastname: Vong
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao, China.
authors.forename: Hisa Hui Ling
authors.initials: HH
authors.lastname: Tseng
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
authors.forename: Yiu Wa
authors.initials: YW
authors.lastname: Kwan
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao, China.
authors.forename: Simon Ming-Yuen
authors.initials: SM
authors.lastname: Lee
mesh_terms: D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D062105:Molecular Docking Simulation / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D047428:Protein Kinase Inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Molecular docking; Pharmacophore modeling; VEGFR2; VEGFR2 inhibitors; Virtual screening