Metal Impurities Cause False Positives in High-Throughput Screening Campaigns
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- 作者：Johannes C. Hermann ; Yingsi Chen ; Charles Wartchow ; John Menke ; Lin Gao ; Shelley K. Gleason ; Nancy-Ellen Haynes ; Nathan Scott ; Ann Petersen ; Stephen Gabriel ; Binh Vu ; Kelly M. George ; Arjun Narayanan ; Shirley H. Li ; Hong Qian ; Nanda Beatini ; Linghao Niu ; Qing-Fen Gan
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：February 14, 2013
- 年：2013
- 卷：4
- 期：2
- 页码：197-200
- 全文大小：183K
- 年卷期：v.4,no.2(February 14, 2013)
- ISSN：1948-5875
文摘
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.