SU6668, a multitargeted angiogenesis inhibitor

Abstract

Angiogenesis plays a critical role in the growth and metastasis of solid and hematologic malignancies. This complex and highly regulated process involves numerous different cell types and mediators. Vascular endothelial growth factor, basic fibroblast growth factor, and platelet-derived growth factor are among the soluble factors that stimulate this process. They are ligands for specific tyrosine kinase receptors that are important in transduction of intracellular signals and induction of angiogenesis. SU6668 is a novel molecule that competitively inhibits the tyrosine kinase of the receptors for vascular endothelial growth factor, basic fibroblast growth factor, platelet-derived growth factor, and c-kit. In vitro studies have confirmed that SU6668 inhibits growth factor-stimulated tyrosine phosphorylation. SU6668 also has significant antitumor activity against many types of tumor xenograft explants in athymic mice. SU6668 inhibits angiogenesis through several mechanisms, including the induction of apoptosis in vascular endothelial cells and tumor cells. Currently, Phase 1 studies are being initiated to evaluate the potential of SU6668 as an anticancer agent for humans.