Molecular design and clinical development of VEGFR kinase inhibitors

Haizhen Zhong, J. Philip Bowen

Research output: Contribution to journalReview articlepeer-review

56 Scopus citations


Vascular angiogenesis has been shown to play a key role in many solid tumors. The vascular endothelial growth factor (VEGF) isoforms and their tyrosine kinase receptors (VEGFRs) have been under intense research for effective anticancer drug candidates. Epidermal growth factor (EGF) and its receptor (EGFR) provide another pathway critical in monitoring angiogenesis. VEGF exerts its effect through binding to tyrosine kinase receptors, mainly VEGFR-1 (Flt-1, the fms-like tyrosine kinase-1) and VEGFR-2 (Flk-1/KDR, fetal liver kinase-1). This paper reviews the progress, mechanism, and binding modes of recently approved kinase inhibitors, such as sunitinib (Sutentr®), sorafenib (Nexavar®) and dasatinib (Sprycel®), as well as other inhibitors that are still under clinical development. Recent clinical treatments suggest that most inhibitors of VEGFR (and/or EGFR) exert their therapeutic effect through not only targeting the VEGFR (and/or EGFR) pathway, but also inhibiting other pathways, such as RAF/MEK/ERK pathway. A new pharmacophore model for second generation of type II tyrosine kinase inhibitors and recent advances in the combination of VEGFR tyrosine kinase inhibitors and other chemotherapeutics are also covered.

Original languageEnglish (US)
Pages (from-to)1379-1393
Number of pages15
JournalCurrent Topics in Medicinal Chemistry
Issue number14
StatePublished - Jul 2007
Externally publishedYes


  • Kinase inhibitor

ASJC Scopus subject areas

  • Drug Discovery


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