Small-molecule discovery through DNA-encoded libraries

The development of bioactive small molecules as probes or drug candidates requires discovery platforms that enable access to chemical diversity and can quickly reveal new ligands for a target of interest. Within the past 15 years, DNA-encoded library (DEL) technology has matured into a widely used p...

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Veröffentlicht in:Nature reviews. Drug discovery Jg. 22; H. 9; S. 699 - 722
Hauptverfasser: Peterson, Alexander A., Liu, David R.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 01.09.2023
Nature Publishing Group
Schlagworte:
631/154/1435
631/92/2132/605
Biomedical and Life Sciences
Biomedicine
Biotechnology
Cancer Research
DNA - chemistry
Drug Discovery - methods
Gene Library
Humans
Ligands
Medicinal Chemistry
Molecular Medicine
Pharmacology/Toxicology
Review Article
Small Molecule Libraries - chemistry
Small Molecule Libraries - pharmacology
ISSN:1474-1776, 1474-1784, 1474-1784
Online-Zugang:Volltext
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Zusammenfassung:The development of bioactive small molecules as probes or drug candidates requires discovery platforms that enable access to chemical diversity and can quickly reveal new ligands for a target of interest. Within the past 15 years, DNA-encoded library (DEL) technology has matured into a widely used platform for small-molecule discovery, yielding a wide variety of bioactive ligands for many therapeutically relevant targets. DELs offer many advantages compared with traditional screening methods, including efficiency of screening, easily multiplexed targets and library selections, minimized resources needed to evaluate an entire DEL and large library sizes. This Review provides accounts of recently described small molecules discovered from DELs, including their initial identification, optimization and validation of biological properties including suitability for clinical applications. DNA-encoded library (DEL) technology is a powerful small-molecule discovery platform, offering many advantages over traditional screening methods. Here, Peterson and Liu provide an in-depth review of recent small molecules discovered through DELs, illustrating the versatility, efficiency and broad impact of this technology.
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ISSN:1474-1776
1474-1784
1474-1784
DOI:10.1038/s41573-023-00713-6