Applications of Receptor-Based NMR Screening in Drug Discovery

High-throughput screening (HTS) of large corporate compound libraries has become the primary strategy for lead generation in the pharmaceutical industry. However, despite the advances in screening and chemistry technologies over the last decade, there has been little increase in the rate of discovery of quality drug leads [1,2]. One of the primary reasons for this problem is the nature of the hits that come from traditional HTS campaigns. Most hits tend to look „drug-like,“ with molecular weights <500 and Clog P values <5, but the optimization process tends to increase both size and hydrophobicityleading to compounds with significantly poorer drug-like properties [3]. An additional problem is the large numbers of false positives that potentially come from HTS campaigns, confounding lead triage and the identification of quality leads that act via the intended mechanism of action [4].