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Development of SU5416, a selective small molecule inhibitor of VEGF receptor tyrosine kinase activity, as an anti-angiogenesis agent

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Angiogenesis, or the sprouting of new blood vessels, is a central process in the growth of solid tumors. For many cancers, the extent of vascularization of a tumor is a negative prognostic indicator signifying aggressive disease and increased potential for metastasis. Recent efforts to understand the molecular basis of tumor-associated angiogenesis have identified several potential therapeutic targets, including the receptor tyrosine kinases for the angiogenic factor vascular endothelial growth factor (VEGF). Here we review the approach taken at SUGEN, Inc. to discover and develop small molecule inhibitors of receptor tyrosine kinases as anti-angiogenic agents. We focus on SU5416, a selective inhibitor of VEGF receptors that is currently in clinical development for the treatment of advanced malignancies. Its biochemical, biological and pharmacological properties are reviewed and clinical implications discussed.
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Keywords: SU5416; angiogenesis; cancer; indolinones

Document Type: Research Article

Affiliations: 1: Corresponding author 2: Department of Surgical Oncology and Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA 3: Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, TX 78245, USA

Publication date: February 1, 2000

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