Inhibition of RNA-binding proteins with small molecules

Protein–RNA interactions have crucial roles in various cellular activities, which, when dysregulated, can lead to a range of human diseases. The identification of small molecules that target the interaction between RNA-binding proteins (RBPs) and RNA is progressing rapidly and represents a novel strategy for the discovery of chemical probes that facilitate understanding of the cellular functions of RBPs and of therapeutic agents with new mechanisms of action. In this Review, I present a current overview of targeting emerging RBPs using small-molecule inhibitors and recent progress in this burgeoning field. Small-molecule inhibitors that were reported for three representative emerging classes of RBPs, the microRNA-binding protein LIN28, the single-stranded or double-stranded RNA-binding Toll-like receptors and the CRISPR-associated (Cas) proteins, are highlighted from a medicinal-chemistry and chemical-biology perspective. However, although this field is burgeoning, challenges remain in the discovery and characterization of small-molecule inhibitors of RBPs. RNA-binding proteins have crucial roles in cellular activities, and disruption of their function is associated with human diseases. This Review describes inhibition of RNA-binding proteins using small molecules as a rapidly evolving strategy for the discovery of chemical probes and therapeutics.