Synthesis and Biological Activity of 2′,2′-Difluorodeoxycytidine (Gemcitabine)

L. W. Hertel, J. S. Kroin, C. S. Grossman, Gerald B. Grindey, A. F. Dorr, A. M.V. Storniolo, W. Plunkett, V. Gandhi, P. Huang

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

GEMZAR® (gemcitabine·HCl) is a difluorinated analog of deoxy cytidine. It was initially synthesized as a novel anti-viral compound with broad spectrum in vitro activity against both RNA and DNA viruses. However, the compound proved to have a narrow therapeutic index when it was administered daily during the in vivo evaluation of antiviral activity. Using a staggered schedule of administration, GEMZAR is found to be a potent antitumor agent in murine and human xenograft solid tumor models. Studies have shown that gemcitabine diphosphate is a ribonucleotide reductase inhibitor, whereas the triphosphate is a potent and unique terminator of DNA synthesis. In phase I studies a variety of dose schedules were investigated. Based on phase I studies including pharmacokinetic data, phase II studies were initiated. Activity was observed in a variety of solid tumors. The results are specially encouraging for non-small cell lung and pancreatic cancer. GEMZAR is currently undergoing registration review of the Phase III clinical trials for treatment of non-small cell lung and pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)265-278
Number of pages14
JournalACS Symposium Series
Volume639
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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    Hertel, L. W., Kroin, J. S., Grossman, C. S., Grindey, G. B., Dorr, A. F., Storniolo, A. M. V., Plunkett, W., Gandhi, V., & Huang, P. (1996). Synthesis and Biological Activity of 2′,2′-Difluorodeoxycytidine (Gemcitabine). ACS Symposium Series, 639, 265-278.