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Screening


CyBio® FeliX Your Automated Application Starts Here


inflammatory diseases and CNS disorders) where the causes may be unknown, and intervention points can be far downstream. Thus, a more com- prehensive understanding of the cell types, biolog- ical processes and tissue responses involved in the disease is required to design successful screening assays. A group from Novartis recently shared their experiences with phenotypic screening over a five-year period, from 2011-1513. In 2011 ~5% of the discovery screens at Novartis were phenotypic- based, rising to a peak of nearly 40% in 2014. This experience led the Novartis team to recommend prosecution of small pilot screens of 1,000-5,000 compounds on multiple assays representing differ- ent aspects of biology in order to select and refine a desired phenotype. Sampling and testing the biol- ogy this way allowed them to advance their under- standing of the disease biology, exploring and refining the therapeutic hypothesis before final assay selection.


Your Automated Application Starts Here CyBio® FeliX


Flexible and compact liquid handling platform for the  volume ranges with additional format possibilities.


Flexible pipettor with 1 – 384 channels and automatic loading of pipetting tools Unique and compact deck design, 12 positions on 2 levels Patent pending CHOICETM from 500 nl –1 ml


technology for pipetting www.analytik-jena.com


Prosecuting phenotypic drug discovery programmes – process considerations The prosecution of target-based drug discovery programmes, having been the subject of intensive process improvement efforts over several decades, follows a more-or-less predictable path, from ini- tial screen and hit identification to lead selection, optimisation, preclinical assessment and clinical candidate selection. The framework for prosecut- ing phenotypic discovery programmes is less well- established. Unlike target-based programmes, hits from phenotypic screens may act through any one of a number of known or unknown targets, and so require mechanistic characterisation to progress. This characterisation is needed to triage hits based on undesirable mechanisms as well as to group hits into similar mechanism classes. Developing an appropriate assay flow scheme of secondary assays for counterscreening for a phenotypic programme requires greater upfront investment than for tar- get-based discovery programmes, and the flow scheme can change as the programme progresses as new information is incorporated.


The first tier of secondary assays is typically identified during assay development from in-depth characterisation studies performed on the selected phenotypic screen. Assay characterisation is ini- tially performed to support the relevance of the system for the purpose of predicting the clinical outcome of interest, for example, through the use of translational biomarkers or disease signatures that can be matched to clinical samples. Once this is established, further interrogation of the assay is performed via perturbation studies using drugs


Drug Discovery World Fall 2017


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