Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/6834
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Title: Development of an oral form of azacytidine : 2′3′5′ triacetyl-5-azacytidine
Authors: Ziemba, A
Hayes, E
Freeman III, BB
Ye, T 
Pizzorno, G
Issue Date: 2011
Source: Chemotherapy research and practice, v. 2011, 965826, p.1-9
Abstract: Myelodysplastic syndromes (MDSs) represent a group of incurable stem-cell malignancies which are predominantly treated by supportive care. Epigenetic silencing through promoter methylation of a number of genes is present in poor-risk subtypes of MDS and often predicts transformation to acute myelogenous leukemia (AML). Azacitidine and decitabine, two FDA-approved DNA methyltransferase (DNMT) inhibitors, are able to improve overall response although their oral bioavailability complicates their clinical use. This study evaluated 2′,3′,5′-triacetyl-5-azacitidine (TAC) as a potential prodrug for azacitidine. The prodrug demonstrated significant pharmacokinetic improvements in bioavailability, solubility, and stability over the parent compound. In vivo analyses indicated a lack of general toxicity coupled with significantly improved survival. Pharmacodynamic analyses confirmed its ability to suppress global methylation in vivo. These data indicate that esterified nucleoside derivatives may be effective prodrugs for azacitidine and encourages further investigation of TAC into its metabolism, activity, and possible clinical evaluation.
Publisher: Hindawi Publishing Corporation
Journal: Chemotherapy research and practice 
ISSN: 2090-2107 (print)
2090-2115 (online)
DOI: 10.1155/2011/965826
Rights: Copyright © 2011 Amy Ziemba et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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