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

Abstract

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.

• Authors: Victor E Marquez, James A Kelley, Riad Agbaria, Tisipi Ben-Kasus, Jonathan C Cheng, Christine B Yoo, Peter A Jones
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1058 Pg. 246-54 (Nov 2005) ISSN: 0077-8923 [Print] United States
• PMID: 16394141 (Publication Type: Journal Article, Review)

Chemical References

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

Topics

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