Zebularine: A Unique Molecule for an Epigenetically Based Strategy in Cancer Chemotherapy

1‐(β‐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.