Investigational New Drugs

, Volume 18, Issue 4, pp 365–371

Preclinical Development of Eniluracil: Enhancing the Therapeutic Index and Dosing Convenience of 5-Fluorouracil


  • Melanie T. Paff
    • Glaxo Wellcome, Inc
  • David P. Baccanari
    • Glaxo Wellcome, Inc
  • Stephen T. Davis
    • Glaxo Wellcome, Inc
  • Shousong Cao
    • Grace Cancer Drug CenterRoswell Park Cancer Institute
  • Robert L. Tansik
    • Glaxo Wellcome, Inc
  • Youcef M. Rustum
    • Grace Cancer Drug CenterRoswell Park Cancer Institute
  • Thomas Spector
    • Spector Consulting Services

DOI: 10.1023/A:1006401432488

Cite this article as:
Paff, M.T., Baccanari, D.P., Davis, S.T. et al. Invest New Drugs (2000) 18: 365. doi:10.1023/A:1006401432488


Eniluracil (5-ethynyluracil, GW 776, 776C85) isbeing developed as a novel modulator of 5-fluorouracil (5-FU) forthe treatment of cancer. Eniluracil is an effective mechanism-based inactivator of dihydropyrimidine dehydrogenase (DPD), thefirst enzyme in the catabolic pathway of 5-FU. By temporarilyeliminating this prevalent enzyme, eniluracil providespredictable dosing of 5-FU and enables oral administration of5-FU to replace intravenous bolus and continuously infuseddosing. New DPD is synthesized with a half-life of 2.6 days. Italso eliminates the formation of problematic 5-FU catabolites.Most importantly, in laboratory animals, eniluracil increases thetherapeutic index and absolute efficacy of 5-FU. Accompanyingreports in this journal indicate that eniluracil has promisingclinical potential.

cancerdihydropyrimidine dehydrogenaseGW 776oral dosinguracil reductase776C85

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© Kluwer Academic Publishers 2000