Phenotypic screening is transforming drug discovery as advances are made in development of human-based physiologically-relevant in vitro systems.
Phenotypic drug discovery (PDD) implies screening where the molecular mechanism of action is not assumed and does not require knowledge of the molecular target.
Flow cytometry has many of the technology attributes (eg multi-parameter analysis of cell suspensions) needed when attempting to profile a phenotypic drug response. However, for flow cytometry to be considered the phenotypic drug screening platform of choice it needs to interface with the real screening world, ie be able to support higher throughput and to acquire low sample volumes from high density microplates.
Renewed awareness of the value of phenotypic screening to drug discovery1-5 creates many new opportunities to increase drug discovery success and productivity. These opportunities include identification of translational phenotypic biomarkers, development of new assays that translate to human disease and refinement of paradigms to successfully execute phenotypic drug discovery (PDD).
The pharmaceutical industry has not seen the hoped-for productivity gains from the various omics datastreams over the last decade.This article discusses how systems biology can exploit the natural interlinkages between these datastreams and put in place a powerful system for modern therapeutic development.