Phenotypic screens as a renewed approach for drug discovery

Abstract

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.

Figure 1

Evolution of drug screening and lead discovery.

Figure 2. Comparisons of phenotypic screen and drug development using drug repurposing screen with the traditional process of drug discovery

(a) Traditional drug discovery usually takes 12 years and costs 1 billion dollars on average to develop a drug. (b) The target does not need to be known for phenotypic based drug discovery and it may or may not be identified after the lead discovery. (c) Drug repurposing screen using phenotypic assays has the potential for rapid drug discovery and development that may not need the prolonged preclinical drug development. The development time and cost in this approach can be much lower compared with the traditional drug discovery. (d) Drug repurposing screen can also be used for new target identification because many active drugs have known mechanism(s) of action. The identified lead compounds that may not be used immediately as a drug for a new indication may point out a new target and direction for drug discovery.