The limitations of small molecule and genetic screening in phenotypic drug discovery

Phenotypic screens carried out with functional genomics or small molecules have led to novel biological insights, revealed previously unknown targets for drug discovery programs, and provided starting points for the development of first-in-class therapies. Despite being valuable research tools, genetic and compound screening also have significant limitations. This perspective aims to shed a light on those limitations and provide mitigation strategies when available, with a goal of helping phenotypic screening practitioners gain an understanding of how and when to best utilize either approach.