Metal Impurities Cause False Positives in High-Throughput Screening Campaigns
Metal Impurities Cause False Positives in High-Throughput Screening Campaigns
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DOI：
10.1021/ml3003296
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发表时间：
2013-02-01
影响因子：
4.2
通讯作者：
Gan, Qing-Fen
中科院分区：
文献类型：
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作者：
Hermann, Johannes C.;Chen, Yingsi;Gan, Qing-Fen
已知化合物库中的有机杂质通常会在新先导化合物的筛选活动中导致假阳性信号，但有机杂质并不能完全解释所有假阳性结果。我们在筛选文库中发现了无机杂质，这些杂质也可以引起各种靶点和/或读出系统的阳性信号，包括生物化学和生物传感器测定。我们深入研究了一个特定项目的锌的例子，并回顾了罗氏的各种HTS筛选，提出了一个简单的计数器筛选，使用螯合剂TPEN来排除锌引起的抑制。
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.