Phenotypic screens as a renewed approach for drug discovery

•Phenotypic screening is a renewed approach for lead discovery.•Phenotypic screen approach may improve the success rate of drug approval.•New drug targets can be identified from phenotypic screening of known drug library.•Patient derived iPS cells can generate better phenotypic cell-based disease models.

The significant reduction in the number of newly approved drugs in the past decade has been partially attributed to failures in discovery and validation of new targets. Evaluation of recently approved new drugs has revealed that the number of approved drugs discovered through phenotypic screens, an original drug screening paradigm, has exceeded those discovered through the molecular target-based approach. Phenotypic screening is thus gaining new momentum in drug discovery with the hope that this approach may revitalize drug discovery and improve the success rate of drug approval through the discovery of viable lead compounds and identification of novel drug targets.