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Increasing throughput in lead optimization in vivo toxicity screens.


Meador, V., Jordan, W. and Zimmermann, J.

Current Opinion in Drug Discovery & Development, 5(1), 72-78 (2002).

Lead optimization requires toxicity screening strategies to select a compound with a high likelihood of successful development. As numerous compounds need to be screened and resources to direct toward any single compound are limited, short turnaround times to generate and interpret data are needed. Utilization of in vivo toxicity screens is necessary for an effective screening strategy, however, if not appropriately implemented, they may consume excessive resources and prolong selection of a developable compound. Optimization of in vivo studies requires identifying effective placement into the screening strategy, selecting the appropriate study designs, implementing processes that allow rapid data generation and interpretation, and understanding the utilities of in vivo data. When implemented, an effective, high-throughput screening strategy will utilize adequate but minimal amounts Of resources, and will prioritize processing near technical time limits. These require generating only the data from which decisions Will be made and can be best achieved using as few animals as possible per study.