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Brief Guide: Experimental strategies for high-quality hit selection from small-molecule screening campaigns.

SLAS Discov. 26, 851-854 (2021)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Small-molecule screening is a powerful approach to identify modulators of either specific biological targets or cellular pathways with phenotypic endpoints. A myriad of assay technologies are available to assess the activity of enzymes, monitor protein-protein interactions, measure transcription factor activity in reporter assays, or detect cellular features and activities using high-content imaging. A common challenge during small-molecule screening is, however, the presence of hit compounds generating assay interference, thereby producing false-positive hits. Thus, efforts are needed to uncover such interferences to prioritize high-quality hits for further analysis. This process encompasses (1) computational approaches to flag undesirable compounds, and (2) the use of experimental approaches like counter, orthogonal, and cellular fitness screens to identify and eliminate artifacts. In this brief guide, we provide an overview for first-time users, highlighting experimental screening strategies to prioritize high-quality bioactive hits from high-throughput screening/high-content screening (HTS/HCS) campaigns.
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Publication type Article: Journal article
Document type Review
Corresponding Author
Keywords Cellular Health ; Counter Assay ; False-positive Exclusion ; High-content Screening ; High-throughput Screening ; Hit Triaging ; Orthogonal Assay; Frequent Hitters; Assay; Identification
ISSN (print) / ISBN 2472-5552
e-ISSN 2472-5560
Journal SLAS Discovery
Quellenangaben Volume: 26, Issue: 7, Pages: 851-854 Article Number: , Supplement: ,
Publisher Sage
Publishing Place Thousand Oaks, Calif.
Non-patent literature Publications
Reviewing status Peer reviewed