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Solubility: Soluble in DMSO at 30 mg/mL, soluble in ethanol at 10 mg/mL with warming, very poorly soluble in water, maximum solubility in plain water is estimated to be about 10-20 µM, buffers, serum, or other additives may increase or decrease the aqueous solubility. Vandetanib inhibits VEGFR-dependent tumor angiogenesis and EGFR- and RET-dependent tumor cell proliferation and survival. Herbst, R.S., et al. 'Vandetanib (ZD6474): an orally available receptor tyrosine kinase inhibitor that selectively targets pathways critical for tumor growth and angiogenesis.' Expert Opin. Investig. Drugs 16: 239-249 (2007). The IC50 values for vandetanib in HT-29 and LoVo cells are 10-80 µM and 3.5-16 µM, respectively, when the exposure times are from 3 days to 18 hours. Azzariti, A., et al. 'Prolonged exposure of colon cancer cells to the epidermal growth factor receptor inhibitor gefitinib (Iressa(TM)) and to the antiangiogenic agent ZD6474: Cytotoxic and biomolecular effects.' World J. Gastroenterol. 12: 5140-5147 (2006). Vandetanib is a potent, orally-active inhibitor of kinase insert domain-containing receptor [KDR/vascular endothelial growth factor receptor (VEGFR) 2] tyrosine kinase activity (IC50 = 40 nM). This compound also inhibits fms-like tyrosine kinase 4 (VEGFR3, IC50 = 110 nM) and epidermal growth factor receptor (EGFR/HER1, IC50 = 500 nM) but shows selectivity relating to a range of other tyrosine and serine-threonine kinases. The activity of vandetanib against KDR tyrosine kinase may explain its potent inhibition of vascular endothelial growth factor A-stimulated human umbilical vein endothelial cell proliferation in vitro (IC50 = 60 nM). Wedge S.R., et al. 'ZD6474 Inhibits Vascular Endothelial Growth Factor Signaling, Angiogenesis, and Tumor Growth following Oral Administration.' Cancer Res. 62: 4645-4655 (2002). Vandetanib dose-dependently inhibited EGFR tyrosine kinase activity with IC50 of 0.25 µM. Vandetanib also inhibited colony formation of seven cancer cell lines in soft agar with IC50's ranging between 0.5 and 1 µM. Ciardiello F., et al. 'Antitumor Effects of ZD6474, a Small Molecule Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, with Additional Activity against Epidermal Growth Factor Receptor Tyrosine Kinase.' Clin. Cancer Res. 9: 1546-1556 (2003).
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