Metal Impurities Cause False Positives in High-Throughput Screening Campaigns
ACS Medicinal Chemistry Letters2012Vol. 4(2), pp. 197–200
Citations Over TimeTop 10% of 2012 papers
Johannes C. Hermann, Yingsi Chen, Charles Wartchow, John G. Menke, Lin Gao, Shelley K. Gleason, Nancy-Ellen Haynes, Nathan A. Scott, Ann Petersen, Stephen Gabriel, Binh Vu, Kelly M. George, Arjun Narayanan, Shirley H. Li, Hong Qian, Nanda Beatini, Linghao Niu, Qing-Fen Gan
Abstract
Organic impurities in compound libraries are known to often cause false-positive signals in screening campaigns for new leads, but organic impurities do not fully account for all false-positive results. We discovered inorganic impurities in our screening library that can also cause positive signals for a variety of targets and/or readout systems, including biochemical and biosensor assays. We investigated in depth the example of zinc for a specific project and in retrospect in various HTS screens at Roche and propose a straightforward counter screen using the chelator TPEN to rule out inhibition caused by zinc.
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