Quantitative Prioritization of Tool Compounds for Phenotypic Screening.
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.
['Wang|Yuan|Y|', 'Jenkins|Jeremy L|JL|']
D001681:Biological Assay D019295:Computational Biology D055808:Drug Discovery D008962:Models, Theoretical D010641:Phenotype D057188:Workflow
Tool compound Phenotypic screen Selectivity Target hypothesis validation Bioactivity data integration Chemical probe