Reverse Phase Protein Arrays elucidate mechanisms-of-action and phenotypic response in 2D and 3D models
Pawlak M, Carragher NO (2017)
Drug Discov Today Technol. 2017 Mar;23:7-16. doi: 10.1016/j.ddtec.2017.05.002. Epub 2017 May 30.
The development of new 2D and 3D phenotypic screening assays combined with high-throughput genomic and proteomic technologies are well placed to advance a new era of molecular pathway informed Phenotypic Drug Discovery. We describe the application of Reverse Phase Protein Array (RPPA) technology to elucidate the mechanism-of-action of small molecules at the post-translational pathway level. We propose that profiling of phenotypic hits and lead molecules in increasingly more complex 3D in vitro and ex vivo models at the post-translational pathway network level represents an effective strategy to both triage and progress the preclinical development of phenotypic screening hits.