Vandetanib (ZD6474)

Cell lines

TT and MZ-CRC-1 cells

Preparation method

The solubility of this compound in DMSO is <10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reaction Conditions

250 nM, 5 days for TT cells 6 days for MZ-CRC-1 cells

Applications

After 5 days of treatment, TT (harboring RET/C634W) cells treated with vehicle numbered 1300×103 and those treated with 250 nM ZD6474 numbered 800×103. MZ-CRC-1 (harboring RET/M918T) cells treated (for 6 days) with vehicle or 250 nM ZD6474 numbered 1144×103 and 712×103 respectively. In TT cells, ZD6474 exerted modest cytotoxicity at doses in the range of its IC50 for the RET kinase. A trypan blue exclusion viability assay confirmed that the compound exerted, instead, cytotoxicity at 1 week of treatment at doses of 1–5 μM.

Animal models

Female BALB/c-nu/nu athymic mice injected with TKKK-Luc and OZ-Luc cells

Dosage form

Oral administration; 50, 25, or 12.5mg/kg; daily

Applications

Mice were randomly divided into four treatment groups, namely vandetanib 50, 25, or 12.5mg/kg per b.w. per day, or vehicle control. Treatment started from the next day and continued for at least 4 weeks. The growth of the TKKK-Luc xenograft was significantly suppressed by vandetanib treatment at a lower dose, 12.5–25 mg/kg, whereas reduction of the OZ-Luc xenograft tumor was observed at a vandetanib dose of 50 mg/kg. At the end of the study, tumor volume was significantly lower in the vandetanib 50 mg/kg group of the OZ-Luc xenograft and in the 12.5–50 mg/kg group of the TKKK-Luc xenograft than in the vehicle-treated control group.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Vitagliano D, De Falco V, Tamburrino A, et al. The tyrosine kinase inhibitor ZD6474 blocks proliferation of RET mutant medullary thyroid carcinoma cells. Endocrine-related cancer, 2011, 18(1): 1-11.

[2] Yoshikawa D, Ojima H, Kokubu A, et al. Vandetanib (ZD6474), an inhibitor of VEGFR and EGFR signalling, as a novel molecular-targeted therapy against cholangiocarcinoma. British journal of cancer, 2009, 100(8): 1257-1266.