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Related Experiment Videos

SU6668, a multitargeted angiogenesis inhibitor.

K Hoekman1

  • 1Department of Medical Oncology, Academisch Ziekenhuis, Vrije Universiteit, Amsterdam, The Netherlands.

Cancer Journal (Sudbury, Mass.)
|January 10, 2002
PubMed
Summary

SU6668, an inhibitor of key growth factor receptors, shows promise in blocking tumor angiogenesis and growth. This novel anticancer agent is now entering human clinical trials.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Angiogenesis is crucial for cancer growth and metastasis, involving various cell types and mediators.
  • Soluble factors like vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) stimulate angiogenesis.
  • These factors signal through specific tyrosine kinase receptors, critical for intracellular signal transduction.

Purpose of the Study:

  • To evaluate SU6668, a novel small molecule inhibitor, as a potential anticancer therapeutic.
  • To investigate SU6668's mechanism of action in inhibiting angiogenesis and tumor growth.

Main Methods:

  • SU6668 was tested for its ability to competitively inhibit tyrosine kinase activity of VEGF, bFGF, PDGF, and c-kit receptors.
  • In vitro studies assessed SU6668's effect on growth factor-stimulated tyrosine phosphorylation.
  • Antitumor activity was evaluated using various tumor xenograft explants in athymic mice.

Main Results:

  • SU6668 demonstrated inhibition of growth factor-stimulated tyrosine phosphorylation in vitro.
  • Significant antitumor activity was observed in multiple tumor xenograft models.
  • SU6668 was shown to inhibit angiogenesis via mechanisms including apoptosis induction in endothelial and tumor cells.

Conclusions:

  • SU6668 effectively inhibits key receptor tyrosine kinases involved in angiogenesis.
  • The compound exhibits significant antitumor efficacy and inhibits angiogenesis through multiple pathways.
  • Phase 1 clinical trials are underway to assess SU6668's safety and efficacy in cancer patients.

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