Vandetanib-d6 Property

storage temp. 

Store at -20°C

solubility 

DMSO: soluble; Methanol: soluble; THF: soluble

form 

A solid

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H302Harmful if swallowed

H360May damage fertility or the unborn child

H373May cause damage to organs through prolonged or repeated exposure

H410Very toxic to aquatic life with long lasting effects

Precautionary statements

P201Obtain special instructions before use.

P202Do not handle until all safety precautions have been read and understood.

P260Do not breathe dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P273Avoid release to the environment.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P308+P313IF exposed or concerned: Get medical advice/attention.

P314Get medical advice/attention if you feel unwell.

P330Rinse mouth.

P391Collect spillage. Hazardous to the aquatic environment

P405Store locked up.

P501Dispose of contents/container to..…

Vandetanib-d6 Chemical Properties,Usage,Production

Description

Vandetanib-d₆ 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 (IC₅₀s = 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 G₀/G₁ 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 IC₅₀ 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).