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Modulating biomolecular condensates: a novel approach to drug discovery
Nature Reviews Drug Discovery ( IF 120.1 ) Pub Date : 2022-08-16 , DOI: 10.1038/s41573-022-00505-4
Diana M Mitrea 1 , Matthäus Mittasch 2 , Beatriz Ferreira Gomes 2 , Isaac A Klein 1 , Mark A Murcko 1
Affiliation  

In the past decade, membraneless assemblies known as biomolecular condensates have been reported to play key roles in many cellular functions by compartmentalizing specific proteins and nucleic acids in subcellular environments with distinct properties. Furthermore, growing evidence supports the view that biomolecular condensates often form by phase separation, in which a single-phase system demixes into a two-phase system consisting of a condensed phase and a dilute phase of particular biomolecules. Emerging understanding of condensate function in normal and aberrant cellular states, and of the mechanisms of condensate formation, is providing new insights into human disease and revealing novel therapeutic opportunities. In this Perspective, we propose that such insights could enable a previously unexplored drug discovery approach based on identifying condensate-modifying therapeutics (c-mods), and we discuss the strategies, techniques and challenges involved.



中文翻译:

调节生物分子凝聚物:药物发现的新方法

在过去的十年中,据报道,被称为生物分子缩合物的无膜组件通过在亚细胞环境中划分具有不同特性的特定蛋白质和核酸,在许多细胞功能中发挥关键作用。此外,越来越多的证据支持这样的观点,即生物分子凝聚物通常通过相分离形成,其中单相系统分层混合成由特定生物分子的凝聚相和稀相组成的两相系统。对正常和异常细胞状态下的凝析油功能以及凝析油形成机制的新认识正在为人类疾病提供新的见解并揭示新的治疗机会。在本视角中,我们提出,这些见解可以实现基于识别冷凝修饰疗法(c-mods)的先前未探索的药物发现方法,并且我们讨论了所涉及的策略、技术和挑战。

更新日期:2022-08-16
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