High Throughput Screening (HTS) Techniques: Applications in Chemical Biology
The rapid testing of chemical libraries for biological activity is the primary aim of high throughput screening (HTS). Advances in HTS have paralleled those in molecular biology, instrumentation and automation, and informatics, and the increased availability of arrayed compound libraries. Sophisticated high sensitivity assays and the associated technologies required to implement these assays in HTS have been largely developed within the pharmaceutical industry for the identification of new chemical matter for drug development. However, HTS approaches are now widely applied to the broader questions within biological research. By way of introduction, we will describe the components of HTS and provide examples of strategies used to identify novel chemtypes for specific biological targets using large chemical libraries. We then will illustrate how more narrowly defined compound collections (e.g., targeted libraries or bioactive compounds) have been profiled against related targets or cell types for the purpose of discovering or defining, compound class/gene family selectivity, off‐target activity or “hidden phenotypes”, toxic fingerprints, or any other relationship between chemical structure and bioactivity. In this way, HTS systems can expand the scope of an experimental hypothesis to address questions of chemical biology, be they at the level of an isolated enzymatic activity or that of a complex cellular phenotype.
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