enhanced affinity and specificity. Inforna defined that C1 can target pre-miR-377, however it also identified eight other miRNA precursors with the A bulge that C1 binds in pre-miR-377 (Fig. ). Such RNAs we have dubbed RNA isoforms. Six of these miRNAs are expressed in HUVECs (Fig. ). Thus, the effect of C1 on the levels of each of the miRNAs was studied. Only levels of miR-377 and miR-421 were affected (40 -50% inhibition) at 5 M. Notably, of the six RNA isoforms, the C1-targetable motif is only present in a functional (Dicer processing) site in pre-miR-421 (Fig. ). These results mirror previous studies that show that the binding of SMIRNAs to functional sites are an important determinant of small molecule selectivity. Because of the dual targeting nature of C1 it is henceforth referred to as Targapre-miR-377/421, (TGP-