A simplified view of fusion protein: RNA helicase protein disruption, the mechanism of action of a new EWS-FL1 targeted molecule, YK-4-279. Because EWS-FLI1 is a disordered protein that precludes standard structure-based small-molecule inhibitor design, a divergent strategy was designed. EWS-FLI1 interaction with RNA helicase A is critical for oncogenesis. YK-4-279 blocks RHA interaction with EWS-FLI1. This protein–protein inhibition induces apoptosis in EWS cells and reduces the growth of EWS orthotopic xenografts.
