Previous studies showed that miR-377 was overexpressed in failing hearts, and bioinformatic analysis revealed that VEGFA is a direct target of miR-377. Further studies revealed that repression of miR-377 by an antisense oligonucleotide derepressed VEGFA and stimulated angiogenesis, validating that inhibition of miR-377's biogenesis using a small molecule is a promising method for stimulating VEGFA expression (Fig. ). Inforna was mined for binders to pre-miR-377's Dicer site, identifying nine novel binders with high fitness from the AstraZeneca collection. The binding affinities of these compounds for a model RNAs containing the 5'AAU/3'U_A bulge were measured and compared to a control RNA in which the bulge was mutated to an AU base pair. These studies showed that compound C1 avidly bound to the RNA with the pre-miR-377 Dicer site (Kd = 65 ± 10 µM) and did not bind to the control RNA. Compound 1's ability to inhibit Dicer processing of pre-miR-377 in vitro. Treatment with C1 inhibited processing by Dicer with an IC50 of 50 ± 10 μM, mirroring its Kd (Fig. ). To assess selectivity of this inhibition, the Dicer processing and C1 binding site was mutated. Pre-miR-377 has two A bulges, one at the Dicer site and another upstream.