The Many Facets of Screening Library Design

Many screening approaches for the discovery of leads active against a target or phenotype co-exist in drug discovery, ranging from the use of low molecular weight fragments with biophysical methods to the evaluation of highly complex natural products in cell-based phenotypic assays. Each screening strategy imposes different requirements on the molecules that are being tested. In this chapter, we discuss design rules for various screening sets routinely used by pharmaceutical companies and/or academic screening facilities. Orthogonal approaches, such as chemically diverse versus biologically diverse libraries or pre-plated versus customized compound sets, are contrasted. Additionally, the goal of a screen can greatly influence the selection of compounds. For example, lead and tool compounds may have fundamentally different molecular properties. A common theme for the design of all compound libraries is their high dependence on computational data analysis and algorithms, making screening set design a chemoinformatics task.