RNA-Protein Interaction Inhibitors Library comprises a total of 2,111 compounds. Protein-RNA interactions play critical roles in various cellular processes, and dysregulation of these interactions can contribute to the development of a range of human diseases. Identifying small molecules that can target the interaction between RNA-binding proteins (RBPs) and RNA has emerged as a rapidly advancing field. This approach represents a novel strategy for discovering chemical probes that can enhance our understanding of the cellular functions of RBPs and potentially lead to the development of therapeutic agents with new mechanisms of action.
Compared to the targeting of other protein classes such as G-protein-coupled receptors, ion channels, and kinases, the development of small-molecule inhibitors for RBPs is a relatively new and evolving field. In addition to directly modulating the biological activities of the target RBPs, small-molecule inhibitors can also be utilized to indirectly modulate the interacting RNAs. This is particularly useful for cases where small molecule modulators for the RNA targets are not available. Additionally, small-molecule inhibitors offer an orthogonal approach to specifically target protein-RNA interactions for which other modulating ligands are already known. Recent advancements in our understanding of the complex regulatory network of protein-RNA interactions and the molecular mechanisms underlying the functions of different classes of RBPs have fueled the development of new biochemical and cellular assays for validating hits. As a result, small-molecule modulators have been reported for many previously challenging RBPs that were considered “unligandable.”
Furthermore, researchers have already identified small-molecule inhibitors for emerging classes of RBPs. This includes miRNA-binding protein LIN28, dsRNA-binding or ssRNA-binding Toll-like receptors (TLRs), and crRNA-binding Cas proteins. The discovery of these inhibitors represents significant progress in the field and highlights the potential for targeting RBPs as a promising therapeutic approach.
