Description
Vandetanib-d
6 is intended for use as an internal standard for the quantification of vandetanib by GC- or LC-MS. Vandetanib is a multi-kinase inhibitor that inhibits VEGFR2, VEGFR3, VEGFR1, EGFR, PDGFRβ, Tie-2, and FGFR1 in cell-free assays (IC
50s = 40, 110, 1,600, 500, 1,100, 2,500, and 3,600 nM, respectively).
1,2 It also binds to 142 additional kinases in a panel of 442 kinases (K
ds = 4.6-7,900 nM). Vandetanib (1 and 2.5 μM) induces apoptosis and cell cycle arrest at the G
0/G
1 phase in GEO colon and OVCAR-3 ovarian cancer cells.
3 It inhibits proliferation of HAK1-B, KYN-2, and Huh7 hepatocarcinoma cells, as well as human umbilical vein endothelial cells (HUVECs), with IC
50 values of 10, 8.1, 9.4, and 7.1 μM, respectively.
4 Vandetanib (200 mg/kg) increases survival and decreases tumor angiogenesis and VEGFR2 levels in a D54MG glioblastoma mouse xenograft model.
5 It reduces tumor growth in a variety of mouse xenograft models, including lung, colon, and breast cancer models, when administered at doses of 25, 50, and 100 mg/kg per day.
1 Formulations containing vandetanib have been used in the treatment of medullary thyroid cancer.
Uses
Vandetanib-d6 is the deuterium labeled Vandetanib. Vandetanib (D6474) is a potent, orally active inhibitor of VEGFR2/KDR tyrosine kinase activity (IC50=40 nM). Vandetanib also has activity versus the tyrosine kinase activity of VEGFR3/FLT4 (IC50=110 nM) and EGFR/HER1 (IC50=500 nM)[1].
References
1. Wedge, S.R., Ogilvie, D.J., Dukes, M., et al.
ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration Cancer Res. 62(16),4645-4655(2002).
2. Davis, M.I., Hunt, J.P., Herrgard, S., et al.
Comprehensive analysis of kinase inhibitor selectivity Nat. Biotechnol. 29(11),1046-1051(2011).
3. Ciardiello, F., Caputo, R., Damiano, V., 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(4),1546-1556(2003).
4. Inoue, K., Torimura, T., Nakamura, T., et al.
Vandetanib, an inhibitor of VEGF receptor-2 and EGF receptor, suppresses tumor development and improves prognosis of liver cancer in mice Clin. Cancer Res. 18(14),3924-3933(2012).
5. Rich, J.N., Sathornsumetee, S., Keir, S.T., et al.
ZD6474, a novel tyrosine kinase inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor, inhibits tumor growth of multiple nervous system tumors Clin. Cancer Res. 11(22),8145-8157(2005).
