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

Sivaraman Dandapani1, Gerard Rosse2, Noel Southall3, Joseph M. Salvino4, Craig J. Thomas3

1 Chemical Biology Platform, The Broad Institute of MIT and Harvard University, Cambridge Massachusetts, 2 Dart NeuroScience, San Diego, California, 3 NIH Chemical Genomics Center, National Human Genome Research Institute, Bethesda, Maryland, 4 Drexel University College of Medicine, Philadelphia, Pennsylvania
Publication Name:  Current Protocols in Chemical Biology
Unit Number:   
DOI:  10.1002/9780470559277.ch110252
Online Posting Date:  September, 2012
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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.

Keywords: small molecule library; high‐throughput screening; chemical biology; drug discovery

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Table of Contents

  • High‐Throughput Screening as a Means to Discover Bioactive Agents
  • Historical Context of Screening Libraries
  • The Need for High‐Quality Screening Libraries
  • Using Cheminformatics Tools/Filters to Craft a Library
  • Specialty Libraries/Methodologies
  • Compound Sourcing
  • Specialty Libraries
  • Compound Management
  • Library QC and Profiling
  • Conclusion
  • Acknowledgements
  • Literature Cited
  • Figures
  • Tables
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