title: Plate-based diversity subset screening: an efficient paradigm for high throughput screening of a large screening file.
abstract: The screening files of many large companies, including Pfizer, have grown considerably due to internal chemistry efforts, company mergers and acquisitions, external contracted synthesis, or compound purchase schemes. In order to screen the targets of interest in a cost-effective fashion, we devised an easy-to-assemble, plate-based diversity subset (PBDS) that represents almost the entire computed chemical space of the screening file whilst comprising only a fraction of the plates in the collection. In order to create this file, we developed new design principles for the quality assessment of screening plates: the Rule of 40 (Ro40) and a plate selection process that insured excellent coverage of both library chemistry and legacy chemistry space. This paper describes the rationale, design, construction, and performance of the PBDS, that has evolved into the standard paradigm for singleton (one compound per well) high-throughput screening in Pfizer since its introduction in 2006.
authors.affiliation: Pfizer Worldwide Research and Development, Sandwich, Kent, UK.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Bell
authors.forename: Joseph
authors.initials: J
authors.lastname: Bradley
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Everett
authors.forename: Michelle
authors.initials: M
authors.lastname: Knight
authors.forename: Jens
authors.initials: J
authors.lastname: Loesel
authors.forename: John
authors.initials: J
authors.lastname: Mathias
authors.forename: David
authors.initials: D
authors.lastname: McLoughlin
authors.forename: James
authors.initials: J
authors.lastname: Mills
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sharp
authors.forename: Christine
authors.initials: C
authors.lastname: Williams
authors.forename: Terence P
authors.initials: TP
authors.lastname: Wood
mesh_terms: D000465:Algorithms; D002460:Cell Line; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D021281:Quantitative Structure-Activity Relationship; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D054852:Small Molecule Libraries
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