title: Vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors: development and validation of predictive 3-D QSAR models through extensive ligand- and structure-based approaches.
abstract: Vascular endothelial growth factor receptor-2, (VEGFR-2), is a key element in angiogenesis, the process by which new blood vessels are formed, and is thus an important pharmaceutical target. Here, 3-D quantitative structure-activity relationship (3-D QSAR) were used to build a quantitative screening and pharmacophore model of the VEGFR-2 receptors for design of inhibitors with improved activities. Most of available experimental data information has been used as training set to derive optimized and fully cross-validated eight mono-probe and a multi-probe quantitative models. Notable is the use of 262 molecules, aligned following both structure-based and ligand-based protocols, as external test set confirming the 3-D QSAR models' predictive capability and their usefulness in design new VEGFR-2 inhibitors. From a survey on literature, this is the first generation of a wide-ranging computational medicinal chemistry application on VEGFR2 inhibitors.
authors.affiliation: Rome Center for Molecular Design, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, P. le A. Moro 5, 00185, Rome, Italy, rino.ragno@uniroma1.it.
authors.forename: Rino
authors.initials: R
authors.lastname: Ragno
authors.forename: Flavio
authors.initials: F
authors.lastname: Ballante
authors.forename: Adele
authors.initials: A
authors.lastname: Pirolli
authors.forename: Richard B
authors.initials: RB
authors.lastname: Wickersham
authors.forename: Alexandros
authors.initials: A
authors.lastname: Patsilinakos
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Hesse
authors.forename: Enrico
authors.initials: E
authors.lastname: Perspicace
authors.forename: Gilbert
authors.initials: G
authors.lastname: Kirsch
mesh_terms: D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D008024:Ligands; D047428:Protein Kinase Inhibitors; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2