Pawlak Michael, Carragher Neil O
NMI TT Pharmaservices, Protein Profiling, Markwiesenstrasse 55, 72770 Reutlingen, Germany.
Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK.
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.
新型二维和三维表型筛选分析方法与高通量基因组和蛋白质组技术的发展，为推进分子途径导向的表型药物发现新时代奠定了良好基础。我们描述了反相蛋白质阵列（RPPA）技术在翻译后途径水平阐明小分子作用机制方面的应用。我们提出，在翻译后途径网络水平上，对越来越复杂的三维体外和离体模型中的表型命中物和先导分子进行分析，是一种对表型筛选命中物进行临床前开发分类和推进的有效策略。
