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

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

Research output: Contribution to journalArticle

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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 - 1996

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gemcitabine
Bioactivity
Tumors
DNA
Cells
Ribonucleotide Reductases
Cytidine
Pharmacokinetics
Diphosphates
RNA
Viruses
Heterografts
Antineoplastic Agents
Antiviral Agents

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

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

Synthesis and Biological Activity of 2′,2′-Difluorodeoxycytidine (Gemcitabine). / Hertel, L. W.; Kroin, J. S.; Grossman, C. S.; Grindey, Gerald B.; Dorr, A. F.; Storniolo, Anna Maria; Plunkett, W.; Gandhi, V.; Huang, P.

In: ACS Symposium Series, Vol. 639, 1996, p. 265-278.

Research output: Contribution to journalArticle

Hertel, LW, Kroin, JS, Grossman, CS, Grindey, GB, Dorr, AF, Storniolo, AM, Plunkett, W, Gandhi, V & Huang, P 1996, 'Synthesis and Biological Activity of 2′,2′-Difluorodeoxycytidine (Gemcitabine)', ACS Symposium Series, vol. 639, pp. 265-278.
Hertel LW, Kroin JS, Grossman CS, Grindey GB, Dorr AF, Storniolo AM et al. Synthesis and Biological Activity of 2′,2′-Difluorodeoxycytidine (Gemcitabine). ACS Symposium Series. 1996;639:265-278.
Hertel, L. W. ; Kroin, J. S. ; Grossman, C. S. ; Grindey, Gerald B. ; Dorr, A. F. ; Storniolo, Anna Maria ; Plunkett, W. ; Gandhi, V. ; Huang, P. / Synthesis and Biological Activity of 2′,2′-Difluorodeoxycytidine (Gemcitabine). In: ACS Symposium Series. 1996 ; Vol. 639. pp. 265-278.
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