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Journal of Biomolecular Screening
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Design of Signal Windows in High Throughput Screening Assays for Drug Discovery

G. Sitta Sittampalam

Technology Core Research Division, Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN 46285

Philip W. Iversen

Statistical & Mathematical Sciences, Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN 46285

Joyce A. Boadt

Technology Core Research Division, Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN 46285

Steven D. Kahl

Technology Core Research Division, Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN 46285

Stuart Bright

Technology Core Research Division, Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN 46285

Joseph M. Zock

Natural Products Research, Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN 46285

William P. Janzen

Sphinx Pharmaceuticals Corporation, A Division of Eli Lilly & Company, 4615 University Drive, Durham, NC 27707

Mark D. Lister

Sphinx Pharmaceuticals Corporation, A Division of Eli Lilly & Company, 4615 University Drive, Durham, NC 27707

High Throughput Screening (HTS) assays are used to rapidly identify promising drug candidates or leads from hundreds of thousands of compounds. Hence, it is important that the assay should be designed to discriminate responses from the active and inactive compounds and the background noise. We introduce the idea of a signal window which provides a degree of separation between signals. This allows one to correctly identify new molecular entities with desired level of activity (called "hits") in the presence of variability. The statistical criteria for setting and calculating signal windows are presented along with illustrative examples. Results show that the ideal signal window should be 2 standard deviations (SD) of the largest signal in screening assays, although a 1 SD window size is the minimum acceptable limit. When signal windows are set below 2 SD, the probability of missing "hits" increases significantly.

Journal of Biomolecular Screening, Vol. 2, No. 3, 159-169 (1997)
DOI: 10.1177/108705719700200306
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