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

被引：67

作者：

Marquez, VE ^{[1
]}

Kelley, JA

Agbaria, R

Ben-Kasus, T

Cheng, JC

Yoo, CB

Jones, PA

机构：

[1] NCI, Canc Res Ctr, Med Chem Lab, NIH, Frederick, MD 21702 USA

[2] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Pharmacol, IL-84105 Beer Sheva, Israel

[3] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Urol, Los Angeles, CA 90089 USA

[4] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Biochem, Los Angeles, CA 90089 USA

[5] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Biol Mol, Los Angeles, CA 90089 USA

来源：

THERAPEUTIC OLIGONUCLEOTIDES: TRANSCRIPTIONAL AND TRANSLATIONAL STRATEGIES FOR SILENCING GENE EXPRESSION | 2005年 / 1058卷

关键词：

zebularine; cytidine deaminase inhibition; DNA methyltrasferase inhibition; antitumor activity; gene reactivation;

D O I：

10.1196/annals.1359.037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：246 / 254

页数：9

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