Advances in the development of novel E3 ubiquitin ligase ligands

VernacularTitle:新型E3泛素连接酶配体开发方法的研究进展
Author: Chen-xi WANG ; Yang LU ; Xiao-wu DONG ; Jin-xin CHE
Publication Type:Research Article
Keywords: ubiquitin-proteasome system; ligand discovery; E3 ubiquitin ligase; interaction
From: Acta Pharmaceutica Sinica 2024;59(11):2926-2940
CountryChina
Language:Chinese
Abstract: The ubiquitin-proteasome system (UPS) is responsible for protein degradation in both normal and pathological states. E3 ligases selectively attach ubiquitin to specific substrates, which is essential for regulating cellular homeostasis. The function of E3 ligases has been associated with a variety of diseases, such as cancer and cardiovascular disease. The discovery of E3 ligands can help regulate E3 ligases, thus expanding new ideas for disease treatment. Targeted protein degradation (TPD) drugs, including proteolysis targeting chimera (PROTAC), have become increasingly popular in recent years due to their dependence on E3 ligands. In this paper, we review the discovery techniques of E3 ligands, including activity-based protein mapping, fragment-based drug discovery, and library-based methods, and briefly introduce the protein interaction detection techniques involved in the ligand discovery techniques, in the hope of providing certain ideas for the future discovery of E3 ligands as well as the treatment of diseases.