AUTHOR=Fang Ye TITLE=Label-free drug discovery JOURNAL=Frontiers in Pharmacology VOLUME=5 YEAR=2014 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2014.00052 DOI=10.3389/fphar.2014.00052 ISSN=1663-9812 ABSTRACT=

Current drug discovery is dominated by label-dependent molecular approaches, which screen drugs in the context of a predefined and target-based hypothesis in vitro. Given that target-based discovery has not transformed the industry, phenotypic screen that identifies drugs based on a specific phenotype of cells, tissues, or animals has gained renewed interest. However, owing to the intrinsic complexity in drug–target interactions, there is often a significant gap between the phenotype screened and the ultimate molecular mechanism of action sought. This paper presents a label-free strategy for early drug discovery. This strategy combines label-free cell phenotypic profiling with computational approaches, and holds promise to bridge the gap by offering a kinetic and holistic representation of the functional consequences of drugs in disease relevant cells that is amenable to mechanistic deconvolution.