High Throughput Screening in the Twenty-First Century

Abstract

High throughput screening (HTS) has become the cornerstone of lead identification for small molecules in drug discovery during the last quarter century. The evolution of the sciences and technologies that have evolved as the foundation of modern HTS campaigns are complex and require multidisciplinary interactions. Innovations in integrated automated systems, reagent systems enabled by molecular biology, computational capabilities, and visualization tools have converged to provide sophisticated tools to HTS practitioners. The success of HTS in an organization does not rest solely with those performing HTS but is critically dependent on the interactions of biology and chemistry members of the multidisciplinary teams throughout the early discovery process. Thus a basic knowledge and understanding of the components and processes of HTS is a necessary requirement for effective communication in planning, executing, and analyzing an HTS campaign. This chapter addresses the key components of HTS campaigns, common approaches, and related issues that should be understood by those engaged in small molecule drug discovery.

Small-Molecule Library Subset Screening as an Aid for Accelerating Lead Identification

“…High-throughput screening (HTS) has become a staple for lead discovery in most small-molecule drug discovery programs. 1,2 Its foundation is the testing of large numbers of compounds in assays designed around target molecules, pathways, or phenotypes believed to be relevant in specific disease conditions. It is very labor intensive and requires significant infrastructure that includes compound libraries, automation, and data analysis in addition to assay development.…”