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基于 DNA 编码文库的高通量筛选 (HPS)。

High-power screening (HPS) empowered by DNA-encoded libraries.

机构信息

Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, USA.

Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, USA.

出版信息

Trends Pharmacol Sci. 2022 Jan;43(1):4-15. doi: 10.1016/j.tips.2021.10.008. Epub 2021 Nov 12.

Abstract

The world is totally dependent on medications. As science progresses, new, better, and cheaper drugs are needed more than ever. The pharmaceutical industry has been predominantly dependent on high-throughput screening (HTS) for the past three decades. Considering that the discovery rate has been relatively constant, can one hope for a much-needed sudden trend uptick? DNA-encoded libraries (DELs) and similar technologies, that have several orders of magnitude more screening power than HTS, and that we propose to group together under the umbrella term of high-power screening (HPS), are very well positioned to do exactly that. HPS also offers novel screening options such as parallel screening, ex vivo and in vivo screening, as well as a new path to druggable alternatives such as proteolysis targeting chimeras (PROTACs). Altogether, HPS unlocks novel powerful drug discovery avenues.

摘要

世界完全依赖药物。随着科学的进步,比以往任何时候都更需要新的、更好的、更便宜的药物。在过去的三十年里,制药行业主要依赖高通量筛选(HTS)。考虑到发现率相对稳定,人们能否期望出现急需的突然趋势上升?DNA 编码库 (DEL) 和类似的技术,其筛选能力比 HTS 高出几个数量级,我们建议将它们归为高通量筛选 (HPS) 的保护伞下,非常适合做到这一点。HPS 还提供了新颖的筛选选项,如平行筛选、体外和体内筛选,以及开辟了新的途径来寻找可成药的替代品,如蛋白水解靶向嵌合体 (PROTAC)。总的来说,HPS 为新药发现开辟了新的有力途径。

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