Sydney L. Rosenblum, Dalia M. Soueid, George Giambasu, Steve Vander Roest, Alexander Pasternak, Erin F. DiMauro, Vladimir Simov and Amanda L. Garner
RSC Medicinal Chemistry 2024
https://pubs.rsc.org/en/content/articlelanding/2024/md/d4md00123k
Dysregulation of the networking of RNA-binding proteins (RBPs) and RNAs drives many human diseases, including cancers, and the targeting of RNA–protein interactions (RPIs) has emerged as an exciting area of RNA-targeted drug discovery. Accordingly, methods that enable the discovery of cell-active small molecule modulators of RPIs are needed to propel this emerging field forward. Herein, we describe the application of live-cell assay technology, RNA interaction with protein-mediated complementation assay (RiPCA), for high-throughput screening to identify small molecule inhibitors of the pre-let-7d–Lin28A RPI. Utilizing a combination of RNA-biased small molecules and virtual screening hits, we discovered an RNA-binding small molecule that can disrupt the pre-let-7–Lin28 interaction demonstrating the potential of RiPCA for advancing RPI-targeted drug discovery.
For the full article see here.