Nicholas, Taylor R.Meng, JingweiGreulich, Benjamin M.Morris, Teresa StevieHollenhorst, Peter C.2021-05-282021-05-282020-09-11Nicholas, T. R., Meng, J., Greulich, B. M., Morris, T. S., & Hollenhorst, P. C. (2020). ­­A high-throughput screen identifies inhibitors of the interaction between the oncogenic transcription factor ERG and the cofactor EWS. PLOS ONE, 15(9), e0238999. https://doi.org/10.1371/journal.pone.02389991932-6203https://hdl.handle.net/1805/26064Aberrant expression of the transcription factor ERG is a key driving event in approximately one-half of all of prostate cancers. Lacking an enzymatic pocket and mainly disordered, the structure of ERG is difficult to exploit for therapeutic design. We recently identified EWS as a specific interacting partner of ERG that is required for oncogenic function. In this study, we aimed to target this specific protein-protein interaction with small molecules. A high-throughput screening (HTS) strategy was implemented to identify potential protein-protein interaction inhibitors. Secondary assays verified the function of several hit compounds, and one lead compound inhibited ERG-mediated phenotypes in prostate cells. This is the first study aimed at targeting the ERG-EWS protein-protein interaction for the development of a small molecule-based prostate cancer therapy.en-USAttribution 4.0 InternationalProstatic NeoplasmsRNA-Binding Protein EWSRecombinant ProteinsCell LineArticle