Frequent hitters: nuisance artifacts in high-throughput screening. Issue 4 (April 2020)

• Record Type: Journal Article
• Authors: Yang, Zi-Yi; He, Jun-Hong; Lu, Ai-Ping; Hou, Ting-Jun; Cao, Dong-Sheng
• Is Part Of: Drug discovery today. Volume 25:Issue 4(2020)
• Page Start: 657
• Page End: 667
• Publication Date: 2020-04
• Subjects: Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2020.01.014
• Languages: English
• ISSNs: 1359-6446

Abstract

Graphical abstract: Highlights: The recognition of frequent hitters remains a challenge in early drug discovery. The commonly underlying mechanisms of frequent hitters are reviewed. Experimental detection techniques and computational prediction models for frequent hitters are introduced. Rational and efficient application of frequent hitters computational models is worthy discussing. Abstract : One of the major challenges in early drug discovery is the recognition of frequent hitters (FHs), that is, compounds that nonspecifically bind to a range of macromolecular targets or false positives caused by various types of assay interferences. In this review, we survey the mechanisms underlying different types of FHs, including aggregators, spectroscopic interference compounds (i.e., luciferase inhibitors and fluorescent compounds), chemical reactive compounds, and promiscuous compounds. We also review commonly used experimental detection techniques and computational prediction models for FH identification. In addition, the rational applications of these computational filters are discussed. It is believed that, with the rational use of FH filters, the efficiency of drug discovery will be significantly improved. Teaser: The recognition of frequent hitters is one of the major challenges in early drug discovery. Here, we discuss underlying mechanisms, experimental detection techniques, computational prediction models and their rational use.