Discussion

Phenotypic drug discovery allows multiple, often unknown but biologically-relevant targets and pathways to be investigated simultaneously. Molecules are selected based upon a desired phenotype, including functional effects on disease-relevant cells, tissues, or even whole organisms. Subsequent identification – or deconvolution – of the targets is a critical step, and if successful can also uncover novel, disease-relevant pathways presenting new opportunities for target-based research. Although target deconvolution has traditionally been a significant hurdle, recent advances in cell microarray technology have dramatically increased the success rates for identifying human plasma membrane protein targets, removing a major bottleneck and accelerating discovery. This presentation explores target deconvolution, providing case examples of how cell microarray technology is used to identify targets for phenotypic antibodies, supporting the development of new compounds with novel modes of action.