Benefits of Strategic Small-Scale Targeted Screening.

High-throughput screening (HTS) is a key technology platform for the discovery of chemical probes and identification of potential drug leads. Once mainly found in industry, HTS is now an integral component of a significant number of academic basic and translational research enterprises. Although the allure of large-scale diversity set-based HTS is substantive, the inherent costs associated with this type of screening strategy are steep and often yield suboptimal return on investment. Perhaps more appealing, and potentially more rewarding, are smaller scale screening strategies using targeted libraries coupled with assays with high-physiological relevance. These "high-physiocontextual"-targeted library screening paradigms, in turn, may have significant impact on the quality of chemical probes and ensuing drug discovery efforts.