Zebularine: a unique molecule for an epigenetically based strategy in cancer chemotherapy

Ann N Y Acad Sci. 2005 Nov;1058:246-54. doi: 10.1196/annals.1359.037.


1-(Beta-d-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine) corresponds structurally to cytidine minus the exocyclic 4-amino group. The increased electrophilic character of its simple aglycon endows the molecule with unique biologic properties as a potent inhibitor of both cytidine deaminase and DNA cytosine methyltransferase. The latter activity makes zebularine a promising antitumor agent that is hydrolytically stable, preferentially targets cancer cells, and shows activity both in vitro and in experimental animals, even after oral administration.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cytidine / analogs & derivatives*
  • Cytidine / pharmacology
  • Cytidine Deaminase / metabolism
  • DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA Methylation
  • Epigenesis, Genetic*
  • Humans
  • Kinetics
  • Models, Chemical
  • Neoplasms / drug therapy*
  • Neoplasms / genetics


  • Antineoplastic Agents
  • Cytidine
  • pyrimidin-2-one beta-ribofuranoside
  • DNA (Cytosine-5-)-Methyltransferases
  • Cytidine Deaminase