Zebularine: a unique molecule for an epigenetically based strategy in cancer chemotherapy.
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.
Marquez
Victor E
VE
Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, NIH, Frederick, Maryland 21702, USA. marquezv@dc37a.nci.nih.gov
Kelley
James A
JA
Agbaria
Riad
R
Ben-Kasus
Tisipi
T
Cheng
Jonathan C
JC
Yoo
Christine B
CB
Jones
Peter A
PA
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003562:Cytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003564:Cytidine Deaminase / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics
D000970:Antineoplastic Agents; D003562:Cytidine; C009131:pyrimidin-2-one beta-ribofuranoside; D004248:DNA (Cytosine-5-)-Methyltransferases; D003564:Cytidine Deaminase