Selecting, Acquiring, and Using Small Molecule Libraries for High‐Throughput Screening

Abstract The selection, acquisition, and use of high‐quality small molecule libraries for screening is an essential aspect of drug discovery and chemical biology programs. Screening libraries continue to evolve as researchers gain a greater appreciation of the suitability of small molecules for specific biological targets, processes, and environments. The decision surrounding the makeup of any given small molecule library is informed by a multitude of variables, and opinions vary on best practices. The fitness of any collection relies upon upfront filtering to avoid problematic compounds, assess appropriate physicochemical properties, install the ideal level of structural uniqueness, and determine the desired extent of molecular complexity. These criteria are under constant evaluation and revision as academic and industrial organizations seek out collections that yield ever‐improving results from their screening portfolios. Practical questions including cost, compound management, screening sophistication, and assay objective also play a significant role in the choice of library composition. This overview attempts to offer advice to all organizations engaged in small molecule screening based upon current best practices and theoretical considerations in library selection and acquisition. Curr. Protoc. Chem. Biol . 4:177‐191 © 2012 by John Wiley & Sons, Inc.