| Literature DB >> 33592188 |
Jayme L Dahlin1, Douglas S Auld2, Ina Rothenaigner3, Steve Haney4, Jonathan Z Sexton5, J Willem M Nissink6, Jarrod Walsh7, Jonathan A Lee8, John M Strelow9, Francis S Willard9, Lori Ferrins10, Jonathan B Baell11, Michael A Walters12, Bruce K Hua13, Kamyar Hadian3, Bridget K Wagner14.
Abstract
Compounds that exhibit assay interference or undesirable mechanisms of bioactivity ("nuisance compounds") are routinely encountered in cellular assays, including phenotypic and high-content screening assays. Much is known regarding compound-dependent assay interferences in cell-free assays. However, despite the essential role of cellular assays in chemical biology and drug discovery, there is considerably less known about nuisance compounds in more complex cell-based assays. In our view, a major obstacle to realizing the full potential of chemical biology will not just be difficult-to-drug targets or even the sheer number of targets, but rather nuisance compounds, due to their ability to waste significant resources and erode scientific trust. In this review, we summarize our collective academic, government, and industry experiences regarding cellular nuisance compounds. We describe assay design strategies to mitigate the impact of nuisance compounds and suggest best practices to efficiently address these compounds in complex biological settings. Published by Elsevier Ltd.Entities:
Keywords: artifacts; chemical biology; drug discovery; high-content screening; high-throughput screening; interference; nuisance compounds; phenotypic drug discovery; phenotypic screening
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Year: 2021 PMID： 33592188 PMCID： PMC7979533 DOI： 10.1016/j.chembiol.2021.01.021
Source DB: PubMed Journal: Cell Chem Biol ISSN： 2451-9448 Impact factor: 8.116