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QSAR in Phenotypic HTS

Jenkins, Jeremy (2012) QSAR in Phenotypic HTS. Molecular Informatics, 31 (6-7). pp. 508-514. ISSN 1868-1743


Understanding how core molecular pathways are dysregulated in disease is fundamental to modern drug discovery Since the 2002 inception of the Novartis Institutes for BioMedical Research, developmental and molecular pathways have provided the basis for a “new grammar” and served as an organizing principle for lead finding. While the revolutions over the last three decades in molecular biology and miniaturized robotics enabled high-throughput screening (HTS) approaches to discover chemical modulators of proteins, “hits” from biochemical HTS do not always possess the required physicochemical properties for activity in vivo. In contrast, pathway assays, such as reporter gene assays or mRNA signatures, provide a means to conduct HTS in a (somewhat) more disease-relevant cellular environment. The compromise, however, is that following dose response assays for hit validation, the challenge remains to characterize the Mechanism-of-Action (MOA) of one or more chemical series. To support a pathways-oriented phenotypic screening framework, it is critical to have an infrastructure of Chemical Genetics technologies to prosecute compound targets. The Chemical Genetics strategy presents both a challenge and an opportunity for evolving QSAR from the original task of scoring compounds for a single target or activity readout to a new role in scoring targets for compounds.

Item Type: Article
Additional Information: A paid open access option is available for this journal.
Keywords: phenotypic screening, Bayesian models, target prediction, cheminformatics
Date Deposited: 13 Oct 2015 13:14
Last Modified: 13 Oct 2015 13:14


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