1. Discovery of telomerase inhibitors: existing strategies and emerging innovations.
- Author
-
Kageler L and Aquilanti E
- Subjects
- Humans, Cryoelectron Microscopy, Neoplasms drug therapy, Drug Design, Telomere metabolism, Oligonucleotides chemistry, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Telomerase antagonists & inhibitors, Telomerase metabolism, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Enzyme Inhibitors therapeutic use, Drug Discovery methods
- Abstract
Telomerase, crucial for maintaining telomere length, is an attractive target for cancer therapy due to its role in cellular immortality. Despite three decades of research efforts, no small-molecule telomerase inhibitors have been clinically approved, highlighting the extensive challenges in developing effective telomerase-based therapeutics. This review examines conventional and emerging methods to measure telomerase activity and discusses existing inhibitors, including oligonucleotides and small molecules. Furthermore, this review highlights recent breakthroughs in structural studies of telomerase using cryo-electron microscopy, which can facilitate improved structure-based drug design. Altogether, advancements in structural methodologies and high-throughput screening offer promising prospects for telomerase-based cancer therapeutic development., (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
- Published
- 2024
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