Vandetanib

• CAT Number: A000467
• CAS Number: 443913-73-3
• Molecular Formula: C₂₂H₂₄BrFN₄O₂
• Molecular Weight: 475.35
• Purity: ≥95%
• Target: VEGFR
• Solubility: Limited solubility
• Storage: 3 years -20C powder
• InChI: InChI=1S/C22H24BrFN4O2/c1-28-7-5-14(6-8-28)12-30-21-11-19-16(10-20(21)29-2)22(26-13-25-19)27-18-4-3-15(23)9-17(18)24/h3-4,9-11,13-14H,5-8,12H2,1-2H3,(H,25,26,27)
• InChIKey: UHTHHESEBZOYNR-UHFFFAOYSA-N
• SMILES: CN1CCC(CC1)COC2=C(C=C3C(=C2)N=CN=C3NC4=C(C=C(C=C4)Br)F)OC

Vandetanib is an orally bioavailable 4-anilinoquinazoline. Vandetanib selectively inhibits the tyrosine kinase activity of vascular endothelial growth factor receptor 2 (VEGF2), thereby blocking VEGF-stimulated endothelial cell proliferation and migration and reducing tumor vessel permeability. This agent also blocks the tyrosine kinase activity of epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that mediates tumor cell proliferation and migration and angiogenesis. Vandetanib was the first drug to be approved by FDA (April 2011) for treatment of late-stage (metastatic) medullary thyroid cancer in adult patients who are ineligible for surgery. Vandetanib was approved in 2011.

Reference

1: Duplomb S, Benoit A, Mechtouff-Cimarelli L, Cho TH, Derbel O, Peix JL, de la Fouchardière C. Unusual Adverse Event With Vandetanib in Metastatic Medullary Thyroid Cancer. J Clin Oncol. 2011 Dec 12. [Epub ahead of print] PubMed PMID: 22162581.2: Langmuir PB, Yver A. Vandetanib for the Treatment of Thyroid Cancer. Clin Pharmacol Ther. 2011 Dec 7. doi: 10.1038/clpt.2011.272. [Epub ahead of print] PubMed PMID: 22158569.3: Ernesto S, Arpin D, Nesme P, Pérol M. Diffuse Interstitial Lung Disease Linked to Vandetanib. Clin Lung Cancer. 2011 Nov 29. [Epub ahead of print] PubMed PMID: 22133289.4: Koch L. Pharmacotherapy: Vandetanib-a new therapeutic option in advanced medullary thyroid cancer. Nat Rev Endocrinol. 2011 Nov 15;8(1):1. doi: 10.1038/nrendo.2011.198. PubMed PMID: 22083086.5: Solomon B, Rischin D. Progress in Molecular Targeted Therapy for Thyroid Cancer: Vandetanib in Medullary Thyroid Cancer. J Clin Oncol. 2011 Oct 24. [Epub ahead of print] PubMed PMID: 22025155.6: Wells SA Jr, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, Baudin E, Elisei R, Jarzab B, Vasselli JR, Read J, Langmuir P, Ryan AJ, Schlumberger MJ. Vandetanib in Patients With Locally Advanced or Metastatic Medullary Thyroid Cancer: A Randomized, Double-Blind Phase III Trial. J Clin Oncol. 2011 Nov 21. [Epub ahead of print] PubMed PMID: 22025146.7: Qi WX, Tang LN, He AN, Shen Z, Yao Y. The role of vandetanib in the second-line treatment for advanced non-small-cell-lung cancer: a meta-analysis of four randomized controlled trials. Lung. 2011 Dec;189(6):437-43. Epub 2011 Oct 11. PubMed PMID: 21986852.8: Ahn J, Wee WR, Lee JH, Hyon JY. Vortex keratopathy in a patient receiving vandetanib for non-small cell lung cancer. Korean J Ophthalmol. 2011 Oct;25(5):355-7. Epub 2011 Sep 20. PubMed PMID: 21976946; PubMed Central PMCID: PMC3178773.9: Giovannetti E, Zucali PA, Assaraf YG, Leon LG, Smid K, Alecci C, Giancola F, Destro A, Gianoncelli L, Lorenzi E, Roncalli M, Santoro A, Peters GJ. Preclinical emergence of vandetanib as a potent antitumour agent in mesothelioma: molecular mechanisms underlying its synergistic interaction with pemetrexed and carboplatin. Br J Cancer. 2011 Nov 8;105(10):1542-53. doi: 10.1038/bjc.2011.400. Epub 2011 Oct 4. PubMed PMID: 21970874.10: Saletti P, Sessa C, De Dosso S, Cerny T, Renggli V, Koeberle D. Phase I dose-finding study of vandetanib in combination with gemcitabine in locally advanced unresectable or metastatic pancreatic adenocarcinoma. Oncology. 2011;81(1):50-4. Epub 2011 Sep 15. PubMed PMID: 21921646.