High content screening as a screening tool in drug discovery.
In most pharmaceutical and biotechnology companies there is a need to always improve the quality of lead candidates. This demand resulted in the use of cell-based screening as a method of choice in drug discovery. High content screening (HCS) is multiplexed, functional cell-based screening. HCS can be used in all aspects of drug discovery as an engine for driving lead discovery. The biological applications of HCS have been implemented in research in signaling, cell shape changes and toxicology. HCS has enabled an insight in the cellular effects of our clinical candidates in multiple cellular phenomena like dual reporter assay, subcellular target translocation and cellular morphology. Discovery of therapeutic protein and small molecule converge on diseases in therapeutic areas such neurological disorders and autoimmune diseases. HCS is used for assay development, primary, secondary screening and toxicology testing. In this chapter, the use of HCS assays in drug discovery is described and highlight the necessary step to set-up successfully these assays for screening.
Nichols
Anthony
A
Molecular Screening and Cell Pharmacology Department, Serono Pharmaceutical Research Institute, Geneva, Switzerland.
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D017930:Genes, Reporter / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D009152:Mutagenicity Tests; D021381:Protein Transport; D046888:Tissue Array Analysis / Q000379:methods*