PT - JOURNAL ARTICLE AU - Nathan P. Coussens AU - John C. Braisted AU - Tyler Peryea AU - G. Sitta Sittampalam AU - Anton Simeonov AU - Matthew D. Hall ED - Gottesman, Michael M. TI - Small-Molecule Screens: A Gateway to Cancer Therapeutic Agents with Case Studies of Food and Drug Administration–Approved Drugs AID - 10.1124/pr.117.013755 DP - 2017 Oct 01 TA - Pharmacological Reviews PG - 479--496 VI - 69 IP - 4 4099 - http://pharmrev.aspetjournals.org/content/69/4/479.short 4100 - http://pharmrev.aspetjournals.org/content/69/4/479.full SO - Pharmacol Rev2017 Oct 01; 69 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.