Multitarget inhibitors derived from crosstalk mechanism involving VEGFR2

Future Med Chem. 2014;6(16):1771-89. doi: 10.4155/fmc.14.112.


Seven VEGFR small-molecule inhibitors have been approved by the US FDA as anticancer drugs, which confirms the therapeutic value of angiogenesis inhibitors. However, much more evidence indicates that VEGFR inhibition alone is usually not sufficient to block the tumor progress. The potential of some agents targeting VEGFR owes partially to the simultaneous inhibition of additional targets in other signaling pathways. In this review, the crosstalk between VEGFR2 and the additional targets in other signaling pathways, such as EGFR, MET, FGFR, PDGFR, c-Kit, Raf, PI3K and HDAC, and the synergistic effects derived from multitarget activities against these crosstalks are discussed. We also briefly describe the multitarget inhibitors in clinical trials or reported in the literature and patents under the different multitarget categories involving VEGFR2.

Publication types

  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Humans
  • Molecular Targeted Therapy*
  • Polypharmacology*
  • Receptor Cross-Talk / drug effects*
  • Signal Transduction / drug effects
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism


  • Small Molecule Libraries
  • Vascular Endothelial Growth Factor Receptor-2