title: Development of SU5416, a selective small molecule inhibitor of VEGF receptor tyrosine kinase activity, as an anti-angiogenesis agent.
abstract: 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.
authors.affiliation: SUGEN, Inc., South San Francisco, CA 94080, USA. dirk-mendel@sugen.com
authors.forename: D B
authors.initials: DB
authors.lastname: Mendel
authors.forename: A D
authors.initials: AD
authors.lastname: Laird
authors.forename: B D
authors.initials: BD
authors.lastname: Smolich
authors.forename: R A
authors.initials: RA
authors.lastname: Blake
authors.forename: C
authors.initials: C
authors.lastname: Liang
authors.forename: A L
authors.initials: AL
authors.lastname: Hannah
authors.forename: R M
authors.initials: RM
authors.lastname: Shaheen
authors.forename: L M
authors.initials: LM
authors.lastname: Ellis
authors.forename: S
authors.initials: S
authors.lastname: Weitman
authors.forename: L K
authors.initials: LK
authors.lastname: Shawver
authors.forename: J M
authors.initials: JM
authors.lastname: Cherrington
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors*; D040262:Receptors, Vascular Endothelial Growth Factor
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D011758:Pyrroles; D017978:Receptors, Growth Factor; C116890:Semaxinib; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor