Barraza Scott J, Bhattacharyya Anuradha, Trotta Christopher R, Woll Matthew G
PTC Therapeutics, Inc., 100 Corporate Court, South Plainfield, NJ, USA.
PTC Therapeutics, Inc., 100 Corporate Court, South Plainfield, NJ, USA.
Drug Discov Today. 2023 Jan;28(1):103431. doi: 10.1016/j.drudis.2022.103431. Epub 2022 Nov 7.
The concept of using small molecules to therapeutically modulate pre-mRNA splicing was validated with the US Food and Drug Administration (FDA) approval of Evrysdi® (risdiplam) in 2020. Since then, efforts have continued unabated toward the discovery of new splicing-modulating drugs. However, the drug development world has evolved in the 10 years since risdiplam precursors were first identified in high-throughput screening (HTS). Now, new mechanistic insights into RNA-processing pathways and regulatory networks afford increasingly feasible targeted approaches. In this review, organized into classes of biological target, we compile and summarize small molecules discovered, devised, and developed since 2020 to alter pre-mRNA splicing.
2020年，美国食品药品监督管理局（FDA）批准Evrysdi®（利司扑兰）后，使用小分子对前体mRNA剪接进行治疗性调节的概念得到了验证。从那时起，人们对发现新的剪接调节药物的努力从未减弱。然而，自利司扑兰前体在高通量筛选（HTS）中首次被发现以来的10年里，药物开发领域已经发生了变化。现在，对RNA加工途径和调控网络的新机制见解提供了越来越可行的靶向方法。在这篇按生物靶点类别组织的综述中，我们汇编并总结了自2020年以来发现、设计和开发的用于改变前体mRNA剪接的小分子。
