Seminars in Oncology
Volume 35 , Pages S3-S5 , June 2008

Vinflunine: Discovery and Synthesis of a Novel Microtubule Inhibitor

  • Jacques Fahy

      Affiliations

    • Institut de Recherche Pierre Fabre, Toulouse, France.
    • Corresponding Author InformationAddress correspondence to Jacques Fahy, PhD, Institut de Recherche Pierre Fabre, 3 rue des Satellites, B.P. 94244, 31432 Toulouse, Cedex 4, France
    • ,
  • Paul Hellier

      Affiliations

    • Institut de Recherche Pierre Fabre, Gaillac, France.
    • ,
  • Fabienne Breillout

      Affiliations

    • Pierre Fabre Oncologie, Boulogne, France.
    • ,
  • Christian Bailly

      Affiliations

    • Institut de Recherche Pierre Fabre, Toulouse, France.

References 

  1. Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer. 2004;4:253–265
  2. Hait WN, Rubin E, Goodin S. Tubulin-targeting agents. Cancer Chemother Biol Response Modif. 2005;22:35–59
  3. Rowinsky EK, Tolcher A. Antimicrotubule agents. In:  DeVita VT,  Hellman S,  Rosenberg SA editor. Cancer principles & practice of oncology. 7th ed.. Philadelphia, PA: Lippincott Williams & Wilkins; 2005;p. 390–416
  4. Noble RL, Beer CT, Cutts JH. Further biological activities of vincaleukoblastine-an alkaloid isolated from Vinca rosea (L.). Biochemical Pharmacology. 1958;1:347–357
  5. Gidding CE, Kellie SJ, Kamps WA, De Graaf SS. Vincristine revisited. Crit Rev Oncol Hematol. 1999;29:267–287
  6. Johnson SA, Harper P, Hortobagyi GN, Pouillart P. Vinorelbine: an overview. Cancer Treat Rev. 1996;22:127–142
  7. Duflos A, Kruczynski A, Barret JM. Novel aspects of natural and modified vinca alkaloids. Curr Med Chem Anticancer Agents. 2002;2:55–70
  8. Hill B. Superior in vivo experimental antitumor activity of vinflunine, relative to vinorelbine, in a panel of human tumor xenografts. Eur J Cancer. 1999;35:512–520
  9. Kruczynski A, Colpaert F, Tarayre JP, Mouillard P, Fahy J, Hill BT. Preclinical in vivo antitumor activity of vinflunine, a novel fluorinated Vinca alkaloid. Cancer Chemother Pharmacol. 1998;41:437–447
  10. Krzakowski M. Phase III study of vinflunine versus docetaxel in patients (pts) with advanced non-small cell lung cancer (NSCLC) previously treated with a platinum-containing regimen. J Clin Oncol. 25(18S):387 (abstr 7511).
  11. Olah GA. Crossing conventional boundaries in half a century of research. J Org Chem. 2005;70:2413–2419
  12. Jacquesy JC, Fahy J. Cancer: superacid generation of new antitumor agents. In:  Torrence PF editors. Biomedical chemistry; applying chemical principles to the understanding and treatment of disease. New York, NY: Wiley-Interscience; 2000;p. 227–246
  13. Fahy J. Modifications in the “upper” velbenamine part of the Vinca alkaloids have major implications for tubulin interacting activities. Curr Pharm Des. 2001;7:1181–1197
  14. Fahy J, Duflos A, Ribet JP, Jacquesy JC, Berrier C, Jouannetaud MP, et al. Vinca alkaloids in superacidic media: a method for creating a new family of antitumor derivatives. J Am Chem Soc. 1997;119:8576–8577
  15. Mangeney P, Andriamialisoa RZ, Lallemand JY, Langlois N, Langlois Y, Potier P. 5′-nor anhydrovinblastine, prototype of a new class of vinblastine derivatives. Tetrahedron. 1979;35:2175–2179
  16. Ribet JP, Zalavari P, Fahy J, Duflos A, Beltran T. Complete assignment of 1H and 13C NMR spectra of vinflunine. Mag Res Chem. 2001;39:43–48
  17. Fabre C, Czaplicki J, Wright M, Hill B, Barret JM, Fahy J, et al. Differential binding to the alpha/beta-tubulin dimer of vinorelbine and vinflunine revealed by nuclear magnetic resonance analyses. Biochem Pharmacol. 2002;64:733–740
  18. Lobert S, Fahy J, Hill BT, Duflos A, Etievant C, Correia JJ. Vinca alkaloid-induced tubulin spiral formation correlates with cytotoxicity in the leukemic L1210 cell line. Biochemistry. 2000;39:12053–12062

 All authors are employees of the Institut de Recherche Pierre Fabre, a private pharmaceutical company supporting the development of vinflunine.

PII: S0093-7754(08)00016-X

doi: 10.1053/j.seminoncol.2008.01.004

Seminars in Oncology
Volume 35 , Pages S3-S5 , June 2008

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