The ubiquitin proteasome system (UPS) presents many opportunities for pharmacological intervention. Key players in the UPS are E3 ubiquitin ligases, responsible for conjugation of ubiquitin to specific cognate substrates. Numbering more than 600 members, these ligases represent the most selective way to intervene within this physiologically important system. This Perspective highlights some of the dedicated medicinal chemistry efforts directed at inhibiting the function of specific single-protein and multicomponent RING-type E3 ubiquitin ligases. We present opportunities and challenges associated with targeting this important class of enzymes.

中文翻译：

---

抑制RING型E3泛素天冬氨酸的药物化学。

泛素蛋白酶体系统（UPS）为药理干预提供了许多机会。UPS中的关键角色是E3遍在蛋白连接酶，负责将遍在蛋白与特定同源底物偶联。这些连接酶有600多个成员，是干预这一重要生理系统的最选择性方法。本观点重点介绍了一些专门的药物化学研究，旨在抑制特定的单蛋白和多组分RING型E3泛素连接酶的功能。我们提出了与靶向这一重要酶相关的机遇和挑战。