Journal of Computer-Aided Molecular Design

, Volume 29, Issue 8, pp 757–776

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

  • Rino Ragno
  • Flavio Ballante
  • Adele Pirolli
  • Richard B. WickershamIII
  • Alexandros Patsilinakos
  • Stéphanie Hesse
  • Enrico Perspicace
  • Gilbert Kirsch
Article

DOI: 10.1007/s10822-015-9859-y

Cite this article as:
Ragno, R., Ballante, F., Pirolli, A. et al. J Comput Aided Mol Des (2015) 29: 757. doi:10.1007/s10822-015-9859-y

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.

Keywords

Vascular endothelial growth factor receptor-2 (VEGFR-2) Structure-based drug design (SBDD) Ligand-based drug design (LBDD) 3-D QSAR Molecular docking 3-D QSAutogrid/R 

Supplementary material

10822_2015_9859_MOESM1_ESM.doc (1.4 mb)
Supplementary material 1 (DOC 1443 kb)

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Rino Ragno
    • 1
    • 2
  • Flavio Ballante
    • 1
    • 3
  • Adele Pirolli
    • 1
  • Richard B. WickershamIII
    • 3
  • Alexandros Patsilinakos
    • 1
    • 2
  • Stéphanie Hesse
    • 4
  • Enrico Perspicace
    • 4
    • 5
  • Gilbert Kirsch
    • 4
  1. 1.Rome Center for Molecular Design, Dipartimento di Chimica e Tecnologie del FarmacoSapienza Università di RomaRomeItaly
  2. 2.Magma Dynamics srl, Dipartimento di Chimica e Tecnologie del FarmacoSapienza Università di RomaRomeItaly
  3. 3.Department of Biochemistry and Molecular BiophysicsWashington University in St. Louis School of MedicineSt. LouisUSA
  4. 4.SRSMC UMR CNRS7565 (former LIMBP)MetzFrance
  5. 5.Genfit, Parc EurasantéLossFrance

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