Taghavi Amirhossein, Springer Noah A, Zanon Patrick R A, Li Yanjun, Li Chenglong, Childs-Disney Jessica L, Disney Matthew D
Department of Chemistry, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology 130 Scripps Way Jupiter FL 33458 USA
Department of Chemistry, The Scripps Research Institute 130 Scripps Way Jupiter FL 33458 USA.
RSC Chem Biol. 2025 Feb 13;6(4):510-527. doi: 10.1039/d4cb00272e. eCollection 2025 Apr 2.
RNA structure plays a role in nearly every disease. Therefore, approaches that identify tractable small molecule chemical matter that targets RNA and affects its function would transform drug discovery. Despite this potential, discovery of RNA-targeted small molecule chemical probes and medicines remains in its infancy. Advances in RNA-focused libraries are key to enable more successful primary screens and to define structure-activity relationships amongst hit molecules. In this review, we describe how RNA-focused small molecule libraries have been used and evolved over time and provide underlying principles for their application to develop bioactive small molecules. We also describe areas that need further investigation to advance the field, including generation of larger data sets to inform machine learning approaches.
RNA结构几乎在每种疾病中都发挥着作用。因此，能够识别可靶向RNA并影响其功能的易处理小分子化学物质的方法将改变药物研发。尽管有这种潜力，但针对RNA的小分子化学探针和药物的发现仍处于起步阶段。聚焦于RNA的文库的进展是实现更成功的初筛以及确定命中分子之间构效关系的关键。在本综述中，我们描述了聚焦于RNA的小分子文库是如何随着时间的推移被使用和发展的，并为其应用于开发生物活性小分子提供了基本原理。我们还描述了该领域需要进一步研究的方向，包括生成更大的数据集以为机器学习方法提供信息。
