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P14031
Strategies for Improving the Impact of High-Throughput Screening Campaigns
Presenter Lisa Elkin, Bristol-Myers Squibb, USA
Additional Authors: K Appiah, K Nowak, K Pike, J Zewinski, R Padmanabha, D Harden, and J O’Connell

The last decade has seen an evolutionary growth in the capacity and throughput of high-throughput screening (HTS).  Miniaturized assay formats, together with advancements in assay, reader, and liquid handling technologies, have enabled rapid screening of compound libraries consisting of millions of compounds.  However, the goal of HTS campaigns is not simply to screen as many compounds as possible as quickly as possible, but rather to advance as many high quality, chemically tractable hits into lead optimization and beyond.  To this end, we employ a number of strategies to improve the impact of information provided from each HTS campaign.  These include (1) Building more robust, reproducible, and predictive assays that minimize artifacts from compound interference; (2) Adopting miniaturized formats and process improvements to screen more quickly and efficiently, thereby freeing resources for hit assessment; (3) Designing and conducting high-throughput mechanism-based or cell-based assays and cross-screens to facilitate rapid prioritization of the large number of hits that sometimes arise after screening over a million compounds against a target.   We will provide examples of the above strategies and demonstrate how continued improvements in the efficiency of HTS, together with robust informatics tools, have enabled us to devote more resources to hit assessment and make a significant impact on the ability to quickly and easily determine what hits have the potential to become true leads.