Vandetanib (ZD6474) is an orallly-bioavailable, ATP-competitive, quinazoline-based inhibitor of VEGFR2 that has been shown to inhibit both VEGF-induced signalling in endothelial cells and tumor-induced angiogenesis. [1] Vandetanib inhibits VEGFR2, VEGFR3, EGFR, and RET at IC50s of 40 nM, 110 nM, 500 nM, and 130 nM, respectively. It has been found to inhibit cell proflieration of VEGFR-stimulated cells (IC50 60 nM) and EGFR-stimulated HUVEC proliferation (IC50 170 nM). [2]

Vandetanib shows robust inhibition of VEGF-stimulated VEGFR2 phosphorylation, Erk-1/2 phosphorylation, as well as endothelial cell proliferation at doses less than 100 nM. [3]

More recently, Vandetanib has been shown to antagonize ABCC1- and ABCG2-mediated MDR by inhibition of transport function. ABCG2, expressed in a wide variety of cancer stem cells, is inhibited by vandetanib, potentially reversing MDR at low concentrations. [4]