Label-free drug discovery.
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.
Biochemical Technologies, Science and Technology Division, Corning Incorporated Corning, NY, USA.
Ye
Y
Fang
cell phenotypic screen; drug safety/toxicity; label-free drug discovery; lead selection; molecular mechanism of action; phenotypic screen; polypharmacology; target identification