Vandetanib

Vandetanib is a potent inhibitor of vascular endothelial growth factor receptor type 2 (VEGFR-2, also known as kinase insert domain-containing receptor [KDR]), epidermal growth factor receptor (EGFR), and RET tyrosine kinases. Vandetanib is also a sub-micromolar inhibitor of vascular endothelial receptor tyrosine kinase type 3. Vandetanib inhibits VEGF-stimulated endothelial cell migration, proliferation, survival, and new ​​​‍​​‍​​​​‍​​‍‍blood vessel formation in in vitro models of angiogenesis. Additionally, vandetanib inhibits the epidermal growth factor (EGF)-stimulated receptor tyrosine kinase in tumour cells and endothelial cells. Vandetanib inhibits EGFR-dependent cell proliferation and cell survival in vitro. Vandetanib also inhibits both active forms of RET, wild-type and the majority of mutated forms, and significantly inhibits proliferation of MTC cell lines in vitro. In vivo, administration of vandetanib reduced tumour cell-induced angiogenesis, tumour vessel permeability, tumour microvessel density, and inhibited tumour growth in a variety of human tumour xenograft models in athymic mice. Vandetanib also inhibited the growth, in vivo, of tumours from MTC xenografts. The mechanism of action of vandetanib in locally advanced or metastatic MTC is not known in detail.