Jixia Wang, Xiuli Zhang, Ye Fang and Xinmiao Liang Pages 3190 - 3200 ( 11 )
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.
label-free cell phenotypic assay, mechanism of action, multi-target screen, polypharmacology, resonant waveguide grating biosensor, electric biosensor.
, , Biochemical Technologies, Science and Technology Division, Corning Incorporated, Corning, New York 14831, USA., Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, China.