通过 DNA 编码文库进行小分子发现。
Small-molecule discovery through DNA-encoded libraries.
机构信息
Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
出版信息
Nat Rev Drug Discov. 2023 Sep;22(9):699-722. doi: 10.1038/s41573-023-00713-6. Epub 2023 Jun 16.
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.
生物活性小分子作为探针或候选药物的开发需要能够获得化学多样性的发现平台，并且能够快速揭示目标的新配体。在过去的 15 年中，DNA 编码文库 (DEL) 技术已经成熟为小分子发现的广泛使用平台，为许多治疗相关靶点产生了各种各样的生物活性配体。与传统筛选方法相比，DEL 具有许多优势，包括筛选效率、易于多重化的靶点和文库选择、最小化评估整个 DEL 和大型文库所需的资源，以及较大的文库规模。本综述提供了最近从 DEL 中发现的小分子的描述，包括它们的初始鉴定、优化和生物特性的验证，包括适合临床应用。
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