In light of the high failure rate of compounds when they are subjected to clinical testing, we are seeing a renaissance in phenotypic screening in drug discovery. However, most phenotypic screening is based on the use of cellular assays and here we debate the advantages and disadvantages of single-cell versus 3D multi-cell analyses.
The phenotypic screening of novel drug candidates determines whether a small molecule (or biologic) exerts the desired pharmacology, either in vitro (isolated cells, organoids, tissues) or in vivo. This functional approach is ‘unbiased’ given that the molecular target, and therefore molecular mechanism of action (MMOA), is only determined following lead identification and preclinical optimisation.
By Dr Richard M. Eglen