Molecular design and clinical development of VEGFR kinase inhibitors

Haizhen Andrew Zhong, J. Philip Bowen

Research output: Contribution to journalReview article

53 Citations (Scopus)

Abstract

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
Volume7
Issue number14
DOIs
StatePublished - Jul 1 2007
Externally publishedYes

Fingerprint

Epidermal Growth Factor Receptor
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2
Phosphotransferases
Receptor Protein-Tyrosine Kinases
Protein-Tyrosine Kinases
Vascular Endothelial Growth Factor A
Critical Pathways
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase Kinases
Therapeutic Uses
Blood Vessels
Tumors
Protein Isoforms
Monitoring
Research
Pharmaceutical Preparations
Neoplasms
Dasatinib
sorafenib

Keywords

  • Kinase inhibitor
  • VEGFR

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Molecular design and clinical development of VEGFR kinase inhibitors. / Zhong, Haizhen Andrew; Bowen, J. Philip.

In: Current Topics in Medicinal Chemistry, Vol. 7, No. 14, 01.07.2007, p. 1379-1393.

Research output: Contribution to journalReview article

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