Targeting RNA-binding proteins with small molecules: Perspectives, pitfalls and bifunctional molecules

RNA-binding proteins (RBPs) play vital roles in organisms through binding with RNAs to regulate their functions. Small molecules affecting the function of RBPs have been developed, providing new avenues for drug discovery. Herein, we describe the perspectives on developing small molecule regulators of RBPs. The following types of small molecule modulators are of great interest in drug discovery: small molecules binding to RBPs to affect interactions with RNA molecules, bifunctional molecules binding to RNA or RBP to influence their interactions, and other types of molecules that affect the stability of RNA or RBPs. Moreover, we emphasize that the bifunctional molecules may play important roles in small molecule development to overcome the challenges encountered in the process of drug discovery.

Automated summary

RNA-binding proteins (RBPs) are crucial for regulating the functions of RNA molecules. Small molecules that can interact with RBPs have been developed as potential drug candidates. This article discusses the perspectives on developing small molecule regulators of RBPs, including small molecules that affect RBP-RNA interactions, bifunctional molecules that target both RNA and RBP, and other molecules that influence the stability of RNA or RBPs. The importance of bifunctional molecules in overcoming challenges in drug discovery is emphasized.