Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 4, Issue 2, Pages 197-200Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ml3003296
Keywords
HTS; false positive; assay interference; Pad4; Jak3; Ras; zinc; promiscuous inhibitor; lead identification
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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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