SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types

SU5416, a novel synthetic compound, is a potent and selective inhibitor of the FIk-1/KDR receptor tyrosine kinase that is presently under evaluation i n Phase I clinical studies for the treatment of human cancers. SU5416 was s hown to inhibit vascular endothelial growth factor-dependent mitogenesis of human endothelial cells without inhibiting the growth of a variety of tumo r cells in vitro. In contrast, systemic administration of SU5416 at nontoxi c doses in mice resulted in inhibition of subcutaneous tumor growth of cell s derived from various tissue origins. The antitumor effect of SU5416 was a ccompanied by the appearance of pale white tumors that were resected from d rug-treated animals, supporting the antiangiogenic property of this agent. These findings support that pharmacological inhibition of the enzymatic act ivity of the vascular endothelial growth factor receptor represents a novel strategy for limiting the growth of a wide variety of tumor types.