title: Metal impurities cause false positives in high-throughput screening campaigns.
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.
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Hermann
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Yingsi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Charles
authors.initials: C
authors.lastname: Wartchow
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: John
authors.initials: J
authors.lastname: Menke
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Lin
authors.initials: L
authors.lastname: Gao
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Shelley K
authors.initials: SK
authors.lastname: Gleason
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Nancy-Ellen
authors.initials: NE
authors.lastname: Haynes
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Nathan
authors.initials: N
authors.lastname: Scott
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Ann
authors.initials: A
authors.lastname: Petersen
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Stephen
authors.initials: S
authors.lastname: Gabriel
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Binh
authors.initials: B
authors.lastname: Vu
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: George
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Arjun
authors.initials: A
authors.lastname: Narayanan
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Shirley H
authors.initials: SH
authors.lastname: Li
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Hong
authors.initials: H
authors.lastname: Qian
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Nanda
authors.initials: N
authors.lastname: Beatini
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Linghao
authors.initials: L
authors.lastname: Niu
authors.affiliation: Discovery Chemistry, Discovery Technologies, and Inflammation Discovery, Roche pRED , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Qing-Fen
authors.initials: QF
authors.lastname: Gan
keywords: HTS; Jak3; Pad4; Ras; assay interference; false positive; lead identification; promiscuous inhibitor; zinc