摘要
RNA-binding proteins(RBPs)constitute central regulators of post-transcriptional gene expression and have been increasingly recognized as critical contributors to the pathogenesis of cancer,neurodegenerative disorders,and autoimmune diseases.However,in contrast to well-established drug targets such as kinases and G protein-coupled receptors,RBPs remain largely underexploited owing to their intrinsic structural heterogeneity,dynamic RNA interactions,and paucity of canonical ligand-binding pockets.In this review,we synthesize current knowledge on the roles of RBPs in disease,outline recent advances in the design of small-molecule modulators,and highlight innovative applications of high-throughput screening and chemical biology approaches for target identification and validation.We further discuss emerging concepts and challenges in translating RBP modulators into therapeutics,providing a forward-looking perspective on how these efforts may reshape small-molecule drug discovery in this evolving field.
基金
supported by grants from the National Natural Science Foundation of China(82574253)
the Natural Science Foundation of Jiangsu Province(BK20231483,China)
the Fundamental Research Funds for the Central Universities(2632025TD01,China).
