Shelat Anang A, Guy R Kiplin
Department of Chemical Biology and Therapeutics, Saint Jude Children's Research Hospital, Memphis, TN 38103, USA.
Curr Opin Chem Biol. 2007 Jun;11(3):244-51. doi: 10.1016/j.cbpa.2007.05.003. Epub 2007 May 23.
The most common methods for discovery of chemical compounds capable of manipulating biological function involves some form of screening. The success of such screens is highly dependent on the chemical materials - commonly referred to as libraries - that are assayed. Classic methods for the design of screening libraries have depended on knowledge of target structure and relevant pharmacophores for target focus, and on simple count-based measures to assess other properties. The recent proliferation of two novel screening paradigms, structure-based screening and high-content screening, prompts a profound rethink about the ideal composition of small-molecule screening libraries. We suggest that currently utilized libraries are not optimal for addressing new targets by high-throughput screening, or complex phenotypes by high-content screening.
发现能够操纵生物功能的化合物的最常见方法涉及某种形式的筛选。此类筛选的成功高度依赖于所检测的化学物质——通常称为文库。设计筛选文库的经典方法依赖于目标结构知识和用于聚焦目标的相关药效团，以及基于简单计数的方法来评估其他性质。最近两种新型筛选范式——基于结构的筛选和高内涵筛选的迅速发展，促使人们对小分子筛选文库的理想组成进行深刻反思。我们认为，目前使用的文库对于通过高通量筛选确定新靶点或通过高内涵筛选分析复杂表型而言并非最佳。
