Protein–protein interactions (PPIs) constitute many potential therapeutic targets for the discovery of new drugs. Given their specificity, PPIs are more challenging to target than other ligands. Thus, finding the best screening process can be difficult. Moreover, PPIs often have no direct accessible activity readout. Therefore, it can be unclear which test to choose for the screening of small molecules targeting PPIs. Given that noncellular assays are the most suitable both as first screening assays and for high-throughput screening (HTS), here we focus on noncellular screening assays. For each assay, we discuss the principles and advantages/drawbacks and provide a recent example. We also highlight the crucial parameters to take into account to select the most suitable assays to screen PPI modulators.

蛋白质-蛋白质相互作用（PPI）构成了许多潜在的新药发现治疗靶点。鉴于其特异性，PPI 比其他配体更具挑战性。因此，找到最佳筛选过程可能很困难。此外，PPI 通常没有直接可访问的活动读数。因此，可能不清楚选择哪种测试来筛选靶向 PPI 的小分子。鉴于非细胞检测最适合作为首次筛选检测和高通量筛选 (HTS)，这里我们重点介绍非细胞筛选检测。对于每个检测，我们讨论了原理和优点/缺点，并提供了一个最近的例子。我们还强调了选择最合适的检测来筛选 PPI 调节剂时要考虑的关键参数。