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Dahlin, J.L.* ; Auld, D.S.* ; Rothenaigner, I. ; Haney, S.* ; Sexton, J.Z.* ; Nissink, J.W.M.* ; Walsh, J.* ; Lee, J.A.* ; Strelow, J.M.* ; Willard, F.S.* ; Ferrins, L.* ; Baell, J.B.* ; Walters, M.A.* ; Hua, B.K.* ; Hadian, K. ; Wagner, B.K.*

Nuisance compounds in cellular assays.

Cell Chem. Bio. 28, 356-370 (2021)
Verlagsversion Postprint Forschungsdaten DOI PMC
Open Access Green
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. Nuisance compounds can waste significant resources by producing promising bioactivities that are attributable to undesirable mechanisms of action. Addressing nuisance compounds is particularly challenging in cellular assays. Dahlin et al. summarize academic, government, and industry experiences with assay design and hit triage to specifically address cellular nuisance compounds.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Korrespondenzautor
Schlagwörter Artifacts ; Chemical Biology ; Drug Discovery ; High-content Screening ; High-throughput Screening ; Interference ; Nuisance Compounds ; Phenotypic Drug Discovery ; Phenotypic Screening; High-throughput Identification; Small-molecule; Natural-products; Cancer-cells; Drug; Interference; Inhibition; Discovery; Stability; Targets
ISSN (print) / ISBN 2451-9448
e-ISSN 2451-9456
Zeitschrift Cell Chemical Biology
Quellenangaben Band: 28, Heft: 3, Seiten: 356-370 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge, Massachusetts
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Toxicology and Pharmacology (TOXI)
Förderungen NIDDK NIH HHS
NHLBI NIH HHS