The development of label-free cellular assays for drug discovery.
BACKGROUND
The need to improve drug research and development productivity continues to drive innovation in pharmacological assays. Technologies that can leverage the advantages of both molecular and phenotypic assays would hold great promise for discovery of new medicines.


METHODS
This article briefly reviews current label-free platforms for cell-based assays and is primarily focused on fundamental aspects of these assays using dynamic mass redistribution technology as an example. The article also presents strategies for relating label-free profiles to molecular modes of actions of drugs.


CONCLUSIONS
Emerging evidence suggests that label-free cellular assays are phenotypic in nature, yet permit molecular mechanistic deconvolution. Together with unique competency in throughput, sensitivity and pathway coverages, label-free cellular assays allow users to screen drugs against endogenous receptors in native cells (including disease relevant primary cells) and determine the molecular modes of action of drug molecules. However, there are challenges for label-free in both basic research and drug discovery: the deconvolution of the cellular and molecular mechanisms for the biosensor signatures of receptor-drug interactions, new methodologies for data analysis and the development of new biosensor technologies. These challenges will need to be met for the wide adoption of these assays in drug discovery.
Biochemical Technologies, Science and Technology Division, Corning, Inc. ,  Corning, NY 14831 ,  USA   fangy2@corning.com.
Ye
Y
Fang