| An Efficient Method for Lead Identification using Iterative Focused Screening |
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Presentation: 2A04 Session: CheminformaticsChristine Brideau, Christopher Bayly, Andy Liaw and Vladimir Svetnik, Merck Frosst Center for Therapeutic Research and Merck Research Laboratories Presenting Author: Christine Brideau, Merck Frosst Canada & Co. - Canada Traditional HTS is a random process with the aim of screening as many structurally distinct compounds as possible. A more efficient approach is to apply focused iterative screening (FIS) for instances where targets do not permit an HTS campaign. The rational is to use a small subset of postulated actives enriched with inactives and a powerful statistical modeling tool, Random Forest, to select a biased test set of molecules from a large compound library. This results in higher quality data by testing samples at 3 doses followed by confirmation of actives before the next round of FIS. Our method rapidly identifies true hits and is more successful than others to reduce the number of screening iterations and test samples. Results from two examples of FIS will be shown and compared with real HTS data to demonstrate our approach increases the hit rate and is successful in identifying novel lead structures. |