RNATACs:通过诱导接近靶向 RNA 的多特异性小分子。

RNATACs: Multispecific small molecules targeting RNA by induced proximity.

机构信息

Induced Proximity Platform, Amgen Research, Thousand Oaks, CA 91320, USA.

Induced Proximity Platform, Amgen Research, Thousand Oaks, CA 91320, USA.

出版信息

Cell Chem Biol. 2024 Jun 20;31(6):1101-1117. doi: 10.1016/j.chembiol.2024.05.006. Epub 2024 Jun 13.

Abstract

RNA-targeting small molecules (rSMs) have become an attractive modality to tackle traditionally undruggable proteins and expand the druggable space. Among many innovative concepts, RNA-targeting chimeras (RNATACs) represent a new class of multispecific, induced proximity small molecules that act by chemically bringing RNA targets into proximity with an endogenous RNA effector, such as a ribonuclease (RNase). Depending on the RNA effector, RNATACs can alter the stability, localization, translation, or splicing of the target RNA. Although still in its infancy, this new modality has the potential for broad applications in the future to treat diseases with high unmet need. In this review, we discuss potential advantages of RNATACs, recent progress in the field, and challenges to this cutting-edge technology.

摘要

RNA 靶向小分子 (rSMs) 已成为一种有吸引力的治疗方法,可以针对传统上难以成药的蛋白质并扩大可成药的空间。在许多创新概念中,RNA 靶向嵌合体 (RNATAC) 代表了一类新型的多特异性、诱导接近的小分子,通过化学方式将 RNA 靶标与内源性 RNA 效应物(如核糖核酸酶 (RNase))拉近。根据 RNA 效应物的不同,RNATAC 可以改变靶 RNA 的稳定性、定位、翻译或剪接。尽管仍处于起步阶段,但这种新的治疗模式具有广泛的未来应用潜力,可用于治疗高未满足需求的疾病。在这篇综述中,我们讨论了 RNATAC 的潜在优势、该领域的最新进展以及对这项前沿技术的挑战。

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