RT Journal Article SR Electronic T1 Small-Molecule Screens: A Gateway to Cancer Therapeutic Agents with Case Studies of Food and Drug Administration–Approved Drugs JF Pharmacological Reviews JO Pharmacol Rev FD American Society for Pharmacology and Experimental Therapeutics SP 479 OP 496 DO 10.1124/pr.117.013755 VO 69 IS 4 A1 Nathan P. Coussens A1 John C. Braisted A1 Tyler Peryea A1 G. Sitta Sittampalam A1 Anton Simeonov A1 Matthew D. Hall A2 Michael M. Gottesman YR 2017 UL http://pharmrev.aspetjournals.org/content/69/4/479.abstract AB High-throughput screening (HTS) of small-molecule libraries accelerates the discovery of chemical leads to serve as starting points for probe or therapeutic development. With this approach, thousands of unique small molecules, representing a diverse chemical space, can be rapidly evaluated by biologically and physiologically relevant assays. The origins of numerous United States Food and Drug Administration–approved cancer drugs are linked to HTS, which emphasizes the value in this methodology. The National Institutes of Health Molecular Libraries Program made HTS accessible to the public sector, enabling the development of chemical probes and drug-repurposing initiatives. In this work, the impact of HTS in the field of oncology is considered among both private and public sectors. Examples are given for the discovery and development of approved cancer drugs. The importance of target validation is discussed, and common assay approaches for screening are reviewed. A rigorous examination of the PubChem database demonstrates that public screening centers are contributing to early-stage drug discovery in oncology by focusing on new targets and developing chemical probes. Several case studies highlight the value of different screening strategies and the potential for drug repurposing.