Targeting VEGF signalling via the neuropilin co-receptor

Drug Discov Today. 2013 May;18(9-10):447-55. doi: 10.1016/j.drudis.2012.11.013. Epub 2012 Dec 8.

Abstract

The blockade of tumour vascularisation and angiogenesis continues to be a focus for drug development in oncology and other pathologies. Historically, targeting vascular endothelial growth factor (VEGF) activity and its association with VEGF receptors (VEGFRs) has represented the most promising line of attack. More recently, the recognition that VEGFR co-receptors, neuropilin-1 and -2 (NRP1 and NRP2), are also engaged by specific VEGF isoforms in tandem with the VEGFRs has expanded the landscape for the development of modulators of VEGF-dependent signalling. Here, we review the recent structural characterisation of VEGF interactions with NRP subdomains and the impact this has had on drug development activity in this area.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Neovascularization, Pathologic / metabolism
  • Neuropilins / chemistry
  • Neuropilins / metabolism*
  • Protein Conformation
  • Receptors, Vascular Endothelial Growth Factor / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Neuropilins
  • Vascular Endothelial Growth Factor A
  • Receptors, Vascular Endothelial Growth Factor