Mining the Potential of Label-Free Biosensors for Seven-Transmembrane Receptor Drug Discovery

Abstract Label-free is a broad term used to describe a number of cutting-edge biosensor technologies that have attracted considerable attention in the area of drug discovery for seven-transmembrane G protein-coupled receptors (GPCRs). Label-free biosensors resolve receptor-mediated responses noninvasively in real time and living cells and do so with high textural information and broad signaling-pathway coverage. They should facilitate studies of the receptor's integrated signal transduction biology intractable to classical assays with single pathway focus. Label-free occupies a privilege niche with respect to mechanistic studies in human native cells—healthy or disease-relevant—and the probing of context-dependent pharmacology in relation to whole biological system efficacy. It is expected that implementation of label-free approaches into the drug discovery process will improve clinical predictability of drug candidates at early stages of discovery research by their exquisite capability to sense whole cellular responses akin to tissue bioassays. Here, we present an overview of promises and challenges this rapidly evolving technology offers to drug screening and we also discuss the prospect of advancing drug discovery.