Chapter Five - High-Throughput Screening

Abstract This review provides an overview of the science of high-throughput screening (HTS) within the pharmaceutical industry and the greater drug discovery community. From its origins in the early 1990s to the current state of the art, key aspects of the process are introduced and described in increasing levels of detail. Examples of technologies employed in the automation of HTS are provided, together with an evaluation of their applicability and limitations. The various detection modalities typically encountered, and their suitability to high-density screening formats (96, 386, 1536, or 3456 well) are described. The increasing importance of informatics in screen design, data interpretation, quality control, and its contribution to the development of future HTS strategies is introduced. Current and future trends of how HTS is employed to meet the changing needs for new drug discovery are explored, including the parallel use of complementary screening modalities to sample diverse chemical matter and identify the best starting points for drug discovery programs.