alexa Troubleshooting and deconvoluting label-free cell phenotypic assays in drug discovery.

Journal of Bioengineering and Bioelectronics

Author(s): Fang Y

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Abstract INTRODUCTION: Central to drug discovery and development is to comprehend the target(s), potency, efficacy and safety of drug molecules using pharmacological assays. Owing to their ability to provide a holistic view of drug actions in native cells, label-free biosensor-enabled cell phenotypic assays have been emerging as new generation phenotypic assays for drug discovery. Despite the benefits associated with wide pathway coverage, high sensitivity, high information content, non-invasiveness and real-time kinetics, label-free cell phenotypic assays are often viewed to be a blackbox in the era of target-centric drug discovery. METHODS: This article first reviews the biochemical and biological complexity of drug-target interactions, and then discusses the key characteristics of label-free cell phenotypic assays and presents a five-step strategy to troubleshooting and deconvoluting the label-free cell phenotypic profiles of drugs. RESULTS: Drug-target interactions are intrinsically complicated. Label-free cell phenotypic signatures of drugs mirror the innate complexity of drug-target interactions, and can be effectively deconvoluted using the five-step strategy. DISCUSSION: The past decades have witnessed dramatic expansion of pharmacological assays ranging from molecular to phenotypic assays, which is coincident with the realization of the innate complexity of drug-target interactions. The clinical features of a drug are defined by how it operates at the system level and by its distinct polypharmacology, ontarget, phenotypic and network pharmacology. Approaches to examine the biochemical, cellular and molecular mechanisms of action of drugs are essential to increase the efficiency of drug discovery and development. Label-free cell phenotypic assays and the troubleshooting and deconvoluting approach presented here may hold great promise in drug discovery and development. Copyright © 2012 Elsevier Inc. All rights reserved. This article was published in J Pharmacol Toxicol Methods and referenced in Journal of Bioengineering and Bioelectronics

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