Quantitative Prioritization of Tool Compounds for Phenotypic Screening

Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1787)

Abstract

Phenotypic screens are increasingly utilized in drug discovery for multiple purposes such as lead and/or tool compound finding, and target discovery. Using potent and selective chemical tool compounds against well-defined targets in phenotypic screens can help elucidate biological processes modulating assay phenotypes. Unfortunately the identification of such tools from large heterogeneous bioactivity databases is nontrivial and there is repeated use of published unselective compounds as phenotypic tools. Here we describe a computational model, the compound-target tool score (TS), which is an evidence-based quantitative confidence metric that can be used to systematically rank tool compounds for targets. The identified selective and nonselective tool compounds have applications in phenotypic assays for target hypothesis validation as well as assay development.

Key words

Chemical probe Tool compound Phenotypic screen Selectivity Target hypothesis validation Bioactivity data integration 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Novartis Institutes for BioMedical Research Inc.CambridgeUSA

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