Potential Telomere-Related Pharmacological Targets

Joseph       Berei; Adam       Eckburg; Edward       Miliavski; Austin    D.    Anderson; Rachel    J.    Miller; Joshua       Dein; Allison    M.    Giuffre; Diana       Tang; Shreya       Deb; Kavya    Sri    Racherla; Meet       Patel; Monica    Saravana    Vela; Neelu       Puri
Abstract

Telomeres function as protective caps at the terminal portion of chromosomes, containing non-coding nucleotide sequence repeats. As part of their protective function, telomeres preserve genomic integrity and minimize chromosomal exposure, thus limiting DNA damage responses. With continued mitotic divisions in normal cells, telomeres progressively shorten until they reach a threshold at a point where they activate senescence or cell death pathways. However, the presence of the enzyme telomerase can provide functional immortality to the cells that have reached or progressed past senescence. In senescent cells that amass several oncogenic mutations, cancer formation can occur due to genomic instability and the induction of telomerase activity. Telomerase has been found to be expressed in over 85% of human tumors and is labeled as a near-universal marker for cancer. Due to this feature being present in a majority of tumors but absent in most somatic cells, telomerase and telomeres have become promising targets for the development of new and effective anticancer therapeutics. In this review, we evaluate novel anticancer targets in development which aim to alter telomerase or telomere function. Additionally, we analyze the progress that has been made, including preclinical studies and clinical trials, with therapeutics directed at telomere-related targets. Furthermore, we review the potential telomere-related therapeutics that are used in combination therapy with more traditional cancer treatments. Throughout the review, topics related to medicinal chemistry are discussed, including drug bioavailability and delivery, chemical structure-activity relationships of select therapies, and the development of a unique telomere assay to analyze compounds affecting telomere elongation.
Keywords: Telomere, Telomerase, Cancer, Shelterin, hTERT, ATM, G-Quadruplex, T-oligo.
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Graphical Abstract

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DOI https://dx.doi.org/10.2174/1568026620666200109114339	Print ISSN 1568-0266
Publisher Name Bentham Science Publisher	Online ISSN 1873-4294
Current Topics in Medicinal Chemistry

Potential Telomere-Related Pharmacological Targets

Abstract

Graphical Abstract

Chemistry Based on Natural Products for Therapeutic Purposes

Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design

Drug Discovery in the Age of Artificial Intelligence

From Biodiversity to Chemical Diversity: Focus of Flavonoids

Current Topics in Medicinal Chemistry

Potential Telomere-Related Pharmacological Targets

Abstract

Graphical Abstract

Call for Papers in Thematic Issues

Chemistry Based on Natural Products for Therapeutic Purposes

Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design

Drug Discovery in the Age of Artificial Intelligence

From Biodiversity to Chemical Diversity: Focus of Flavonoids

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