Lead Discovery & Profiling, Discovery Sciences, Janssen R&D LLC, Spring House, Pennsylvania.
Curr Protoc Chem Biol. 2020 Mar;12(1):e78. doi: 10.1002/cpch.78.
Small-molecule drug discovery can be hindered by the formation of aggregates that act as non-selective inhibitors of drug targets. Such aggregates appear as false positives in high-throughput screening campaigns and can bedevil structure-activity relationships during compound optimization. Protocols are described for resonant waveguide grating (RWG) and dynamic light scattering (DLS) as microplate-based high-throughput approaches to identify compound aggregation. Resonant waveguide grating and dynamic light scattering give equivalent results for the compound test set, as assessed with Bland-Altman analysis. © 2019 The Authors. Basic Protocol 1: Resonant waveguide grating (RWG) in 384-well or 1536-well plate format to detect compound aggregation Basic Protocol 2: Dynamic light scattering (DLS) in 384-well plate format to detect compound aggregation.
小分子药物的发现可能会受到聚集体的阻碍，这些聚集体会充当药物靶点的非选择性抑制剂。在高通量筛选实验中，此类聚集体可能会出现假阳性结果，并且在化合物优化过程中会影响结构-活性关系。本文描述了使用谐振波导光栅（RWG）和动态光散射（DLS）作为基于微孔板的高通量方法来鉴定化合物聚集的方法。通过 Bland-Altman 分析评估，谐振波导光栅和动态光散射对化合物测试集给出了等效的结果。© 2019 作者。 基本方案 1：在 384 孔或 1536 孔板格式中使用谐振波导光栅（RWG）检测化合物聚集 基本方案 2：在 384 孔板格式中使用动态光散射（DLS）检测化合物聚集。
