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Plate-based diversity subset screening: an efficient paradigm for high throughput screening of a large screening file |
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| Authors: | Andrew S Bell Joseph Bradley Jeremy R Everett Michelle Knight Jens Loesel John Mathias David McLoughlin James Mills Robert E Sharp Christine Williams Terence P Wood |
| Institution: | 1. Pfizer Worldwide Research and Development, Sandwich, Kent, UK 2. Imperial College, London, UK 3. Scitegrity Ltd, Discovery Park, Sandwich, Kent, UK 4. University of Greenwich, Chatham Maritime, Kent, UK 5. Canterbury Christchurch University, Canterbury, Kent, UK 6. Peter Fisk Associates Limited, Canterbury, Kent, UK 7. Pfizer Research, Cambridge, MA, USA 8. Eli Lilly & Company, Indianapolis, IN, USA 9. Sandexis, Canterbury, Kent, UK 10. Pfizer Worldwide Research & Development, Groton, CT, USA 11. Intrexon Corporation, San Carlos, CA, USA 12. Kent and Canterbury Hospital, Canterbury, Kent, UK 13. TP & AAW Consultancy, Cliftonville, Kent, UK |
| 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. |
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