Phenotypic Screening in Drug Discovery

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28 September 2015



In the past few years, there has been a revival of phenotypic screening for hit discovery and profiling. It is generally accepted that overexpression of targets in heterologous systems has a risk of creating functional artefacts, and in principle, such an assay is single-target focused.

As the understanding of the complex interplay of networks and pathways within cellular processes increases, the need for ways to screen compounds in the correct disease context also grows.

Now practitioners are starting to appreciate polypharmacology and can also harness the knowledge gained from clinical genetics using human primary cells from patients, drug discovery research and high-throughput screening is going through the next paradigm shift. Charles Rivers Laboratories now offers customized assay development, along with screening with readouts including high-content screening and multiparameter analyte or biomarker detection.

This webinar reviews a case study of one such phenotypic screen. In this project, 13 human primary-cell-based assays were developed, either from healthy control donors or from donors with rheumatoid arthritis (RA), idiopathic pulmonary fibrosis (IPF) or type 2 diabetes (T2D). A screen of 1,600 compounds in each of these phenotypic assays not only provided valuable starting points for further optimisation of the compounds, but also highlighted which assays in inflammation, fibrosis and metabolic syndrome help identify unique mechanisms of action.

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