Noncellular screening for the discovery of protein–protein interaction modulators. Issue 9 (September 2020)

• Record Type: Journal Article
• Authors: Kieffer, Charline; Jourdan, Jean Pierre; Jouanne, Marie; Voisin-Chiret, Anne Sophie
• Is Part Of: Drug discovery today. Volume 25:Issue 9(2020)
• Page Start: 1592
• Page End: 1603
• Publication Date: 2020-09
• Subjects: Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2020.07.012
• Languages: English
• ISSNs: 1359-6446

Abstract

Highlights: Screening process of PPIs modulators is challenging. Non-cellular assays are employed for HTS and for a first line of screening process. High throughput assays are available in a mix-and-read format. Low throughput assays require immobilization (SPR, BLI) or not (ITC, MST). Best screening process combines different methods in an orthogonal assay. Abstract : 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. Teaser: We discuss which tests to choose for the screening of small molecules targeting protein–protein interactions.