Patel Avinash, Mitrea Diana, Namasivayam Vigneshwaran, Murcko Mark A, Wagner Michael, Klein Isaac A
Dewpoint Therapeutics GmbH, Dresden, Germany.
Dewpoint Therapeutics, Boston, MA, United States.
Front Mol Biosci. 2022 Nov 22;9:1007744. doi: 10.3389/fmolb.2022.1007744. eCollection 2022.
Biomolecular condensates are compartmentalized communities of biomolecules, which unlike traditional organelles, are not enclosed by membranes. Condensates play roles in diverse cellular processes, are dysfunctional in many disease states, and are often enriched in classically "undruggable" targets. In this review, we provide an overview for how drugs can modulate condensate structure and function by phenotypically classifying them as dissolvers (dissolve condensates), inducers (induce condensates), localizers (alter localization of the specific condensate community members) or morphers (alter the physiochemical properties). We discuss the growing list of bioactive molecules that function as condensate modifiers (c-mods), including small molecules, oligonucleotides, and peptides. We propose that understanding mechanisms of condensate perturbation of known c-mods will accelerate the discovery of a new class of therapies for difficult-to-treat diseases.
生物分子凝聚物是生物分子的区室化群落,与传统细胞器不同,它们没有被膜包围。凝聚物在多种细胞过程中发挥作用,在许多疾病状态下功能失调,并且通常富含经典的“不可成药”靶点。在这篇综述中,我们概述了药物如何通过将它们表型分类为溶解剂(溶解凝聚物)、诱导剂(诱导凝聚物)、定位剂(改变特定凝聚物群落成员的定位)或形态调节剂(改变物理化学性质)来调节凝聚物的结构和功能。我们讨论了越来越多作为凝聚物调节剂(c-mods)发挥作用的生物活性分子,包括小分子、寡核苷酸和肽。我们提出,了解已知c-mods对凝聚物的扰动机制将加速发现一类针对难治性疾病的新型疗法。