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蛋白质-RNA 相互作用的小分子调节剂。

Small-molecule modulators of protein-RNA interactions.

机构信息

CRI Center for Chemical Proteomics, Department of Chemistry, Seoul National University, Seoul, 08826, Korea(South).

School of Biopharmaceutical and Medical Sciences, Sungshin University, Seoul, 01133, Korea(South).

出版信息

Curr Opin Chem Biol. 2022 Jun;68:102149. doi: 10.1016/j.cbpa.2022.102149. Epub 2022 May 6.

Abstract

Protein-RNA interactions (PRIs) play crucial roles in diverse cellular pathways, from transcription to liquid-liquid phase separation, and its dysregulation is associated with a wide range of human disorders. Therefore, there is great emphasis on discovering small-molecule modulators that target unexplored PRIs by developing robust PRI assays. In particular, targeting PRIs could offer innovative solutions to expand the druggable genome, as only a small portion of protein-coding genes are currently targeted by drugs. This review describes the therapeutic potential of targeting PRIs using small molecules, biochemical and cell-based experimental tools for observing PRIs, and several PRI modulators. We also highlight emerging technologies and the challenges in developing PRI modulators.

摘要

蛋白质- RNA 相互作用(PRIs)在从转录到液-液相分离等多种细胞途径中发挥着关键作用,其失调与广泛的人类疾病有关。因此,人们非常重视通过开发强大的 PRI 测定法来发现针对未探索 PRIs 的小分子调节剂。特别是,通过靶向 PRIs 可以提供创新的解决方案来扩大可用药基因组,因为目前只有一小部分编码蛋白质的基因是药物的靶点。这篇综述描述了使用小分子靶向 PRIs 的治疗潜力,以及用于观察 PRIs 的生化和基于细胞的实验工具,以及几种 PRI 调节剂。我们还强调了新兴技术和开发 PRI 调节剂的挑战。

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