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BioDrugs

Erschienen in:

01.08.2011 | Review Article

The Application of Delivery Systems for DNA Methyltransferase Inhibitors

verfasst von: Ms Sue Ping Lim, Paul Neilsen, Raman Kumar, Andrew Abell, David F. Callen

Erschienen in: BioDrugs | Ausgabe 4/2011

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Abstract

DNA methylation, which often occurs at the cytosine residue of cytosine-guanine dinucleotides, is critical for the control of gene expression and mitotic inheritance in eukaryotes. DNA methylation silences gene expression either by directly hindering the access of transcription factors to the target DNA, or through recruitment of histone deacetylases to remodel the chromatin structure to an inactive state. Aberrant hypermethylation of tumor suppressor genes is commonly associated with the development of cancer. A number of anti-cancer agents have been developed that function through demethylation, reversing regional hypermethylation to restore the expression of tumor suppressor genes. Azacitidine and decitabine are used in the clinic, but their applications are limited to myelodysplastic syndrome and other blood-related diseases. Despite the potency of these drugs, their broader clinical application is restricted by cytotoxicity, nonspecific targeting, structural instability, catabolism, and poor bioavailability. Further improvements in the delivery systems for these drugs could overcome the issues associated with inefficient bioavailability, whilst facilitating the administration of combinations of demethylating agents and histone deacetylase inhibitors to enhance efficacy. This review focuses on the current limitations of existing demethylating agents and highlights possible approaches using recent developments in drug delivery systems to improve the clinical potential of these drugs.

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Titel: The Application of Delivery Systems for DNA Methyltransferase Inhibitors
verfasst von: Ms Sue Ping Lim
Paul Neilsen
Raman Kumar
Andrew Abell
David F. Callen
Publikationsdatum: 01.08.2011
Verlag: Springer International Publishing
Erschienen in: BioDrugs / Ausgabe 4/2011
Print ISSN: 1173-8804
Elektronische ISSN: 1179-190X
DOI: https://doi.org/10.2165/11592770-000000000-00000

Springer Medizin

Abstract

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