Abstract
Telomerase is a cellular ribonucleoprotein reverse transcriptase responsible for the maintenance of telomeres, the tandemly repeating guanine-rich nucleic acid sequences at the 3-ends of eukaryotic chromosomes that serve to protect chromosomal stability and maintain integrity. Telomerase enzyme activity is essential for the sustained proliferation of most immortal cells, including cancer cells, and is currently an important recognised target for the development of novel and potentially tumour-specific anticancer chemotherapeutics. Herein, we review recent advances in the design and development of telomerase inhibitors for the treatment of cancer. To date, these have included antisense strategies, reverse transcriptase inhibitors, and agents capable of interacting with high-order telomeric DNA tetraplex (or “G-quadruplex”) structures in such a way as to prevent enzyme access to its required linear telomeric DNA substrate. Critical appraisal of each distinct approach is provided together with highlighted areas for continued development necessary to further refine the present disparate classes of telomerase inhibitors for use in clinically viable therapies.
Keywords: telomerase inhibitr cancer, ribonucleoprotein reverse transcriptase, reverse transcriptase inhibitor
Current Pharmaceutical Design
Title: Design of Telomerase Inhibitors for the Treatment of Cancer
Volume: 8 Issue: 27
Author(s): Donald Cairns, Rosaleen J. Anderson, Philip J. Perry and Terence C. Jenkins
Affiliation:
Keywords: telomerase inhibitr cancer, ribonucleoprotein reverse transcriptase, reverse transcriptase inhibitor
Abstract: Telomerase is a cellular ribonucleoprotein reverse transcriptase responsible for the maintenance of telomeres, the tandemly repeating guanine-rich nucleic acid sequences at the 3-ends of eukaryotic chromosomes that serve to protect chromosomal stability and maintain integrity. Telomerase enzyme activity is essential for the sustained proliferation of most immortal cells, including cancer cells, and is currently an important recognised target for the development of novel and potentially tumour-specific anticancer chemotherapeutics. Herein, we review recent advances in the design and development of telomerase inhibitors for the treatment of cancer. To date, these have included antisense strategies, reverse transcriptase inhibitors, and agents capable of interacting with high-order telomeric DNA tetraplex (or “G-quadruplex”) structures in such a way as to prevent enzyme access to its required linear telomeric DNA substrate. Critical appraisal of each distinct approach is provided together with highlighted areas for continued development necessary to further refine the present disparate classes of telomerase inhibitors for use in clinically viable therapies.
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Cite this article as:
Cairns Donald, Anderson J. Rosaleen, Perry J. Philip and Jenkins C. Terence, Design of Telomerase Inhibitors for the Treatment of Cancer, Current Pharmaceutical Design 2002; 8 (27) . https://dx.doi.org/10.2174/1381612023392720
DOI https://dx.doi.org/10.2174/1381612023392720 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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