4.8 Review

Small-molecule discovery through DNA-encoded libraries

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NATURE REVIEWS DRUG DISCOVERY
卷 22, 期 9, 页码 699-722

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NATURE PORTFOLIO
DOI: 10.1038/s41573-023-00713-6

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DNA-encoded library (DEL) technology is a powerful small-molecule discovery platform, offering many advantages over traditional screening methods. This Review provides accounts of recently described small molecules discovered from DELs, illustrating the versatility, efficiency and broad impact of this technology.
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. 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.

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