Abstract
Background: Most drugs exert their biological and physiological effects via binding to protein targets. Although drugs are traditionally optimized against a single protein, most marketed drugs exhibit clinically relevant polypharmacology – the activity of drugs at multiple targets. The wide-spread presence of polypharmacology makes it challenging to assess the mechanisms of action of multi-target drugs. Methods: This paper first reviews approaches for discovering multi-targets of drug molecules, then discusses key characteristics of label-free cell phenotypic assays, and finally focuses on how to use these assays to assess drug polypharmacology. Results: labelfree cell phenotypic assays have ability to provide a holistic view of drug action in living cells with wide phenotype/ target/pathway coverage, and permit effective deconvolution of the action of multi-target drugs at the whole cell level. Conclusion: Label-free cell phenotypic assays hold great potential in assessing drug polypharmacology.
Keywords: label-free cell phenotypic assay, mechanism of action, multi-target screen, polypharmacology, resonant waveguide grating biosensor, electric biosensor.
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