Institute of Pharmaceutical Sciences, University of Freiburg, Albertstraße 25, Freiburg, 79104, Germany.
Institute of Pharmaceutical Chemistry, Martin-Luther University of Halle-Wittenberg, Wolfgang-Langenbeckstraße 4, Halle/Saale, 06120, Germany.
Curr Opin Chem Biol. 2020 Aug;57:8-16. doi: 10.1016/j.cbpa.2020.01.010. Epub 2020 Mar 5.
Proteolysis targeting chimeras (PROTACs) are heterobifunctional molecules and allow selective protein degradation by addressing the natural ubiquitin proteasome system. As this new strategy of chemically induced protein degradation can serve as a biological tool and provides new possibilities for drug discovery, it has been applied to a variety of targets including (nuclear) receptors, kinases, and epigenetic proteins. A lot of PROTACs have already been designed in the field of epigenetics, and their synthesis and characterization highly contributed to structural optimization and improved mechanistic understanding of these molecules. In this review, we will discuss and summarize recent advances in PROTAC discovery with focus on epigenetic targets.
蛋白水解靶向嵌合体（PROTACs）是一种杂双功能分子，通过靶向天然的泛素蛋白酶体系统来实现选择性蛋白降解。由于这种化学诱导蛋白降解的新策略可以作为一种生物工具，并为药物发现提供新的可能性，因此它已被应用于多种靶点，包括（核）受体、激酶和表观遗传蛋白。在表观遗传学领域已经设计了大量的 PROTACs，它们的合成和表征极大地促进了这些分子的结构优化和对其作用机制的深入理解。在本文中，我们将讨论和总结 PROTAC 发现的最新进展，重点关注表观遗传靶点。
