Philinopside E, a new sulfated saponin from sea cucumber, blocks the interaction between kinase insert domain-containing receptor (KDR) and αvβ3 integrin via binding to the extracellular domain of KDR

Vascular endothelial growth factor ( VEGF) signaling pathway is essential for tumor angiogenesis and has long been recognized as a promising target for cancer therapy. Current view holds that physical interaction between alpha(v) beta(3) integrin and kinase insert domaincontaining receptor ( KDR) is important in regulating angiogenesis and tumor development. We have reported previously that a new marine- derived compound, philinopside E ( PE), exhibited the antiangiogenic activity via inhibition on KDR phosphorylation and downstream signaling. Herein, we have further demonstrated that PE specifically interacts with KDR extracellular domain, which is distinct from conventional small- molecule inhibitors