Adding value to NMR-based fragment screens by using competition binding or functional assays

ANYL 243

Brian J. Stockman, Exploratory Medicinal Chemistry, Pfizer, Inc, 558 Eastern Point Road, 118 267 NMR Lab 4101, Groton, CT 06340
Fragment screening by NMR methods typically yields a list of compounds that bind to the target of interest. These initial hits may or may not bind in the desired active site and may or may not possess inhibitory activity. Conducting the NMR screen using competition methods or by direct functional readout, however, results in a list of hits that bind at the desired active site and/or inhibit function. Importantly, the added value of these hits is obtained with higher throughput compared to direct binding methods.