Evidently, selectivity and potency are indeed possible as now several SMIRNAs have been designed to affect RNA-mediated biology in cells and pre-clinical models of disease. It is likely that as more information emerges on the RNA folds that are bound by small molecules that the number of targets that can be affected by SMIRNAs will increase. In the current study, we designed TGP-377 as a test case to develop approaches to drug a pre-defined RNA target rationally and predictably. A lead compound was quickly identified and then rapidly optimized. Translating lead compounds such as TGP-377 into medicines that reach patients is a more complicated endeavor, however.