Laboratory of Human Diseases and Immunotherapies, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China; Institute of Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
Laboratory of Human Diseases and Immunotherapies, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China; Institute of Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China; Cardiovascular Surgery Research Laboratory, West China Hospital, Sichuan University, Chengdu, 610041, China.
Eur J Med Chem. 2024 Jan 5;263:115950. doi: 10.1016/j.ejmech.2023.115950. Epub 2023 Nov 16.
Molecular glues can specifically induce interactions between two or more proteins to modulate biological functions and have been proven to be a powerful therapeutic modality in drug discovery. It plays a variety of vital roles in several biological processes, such as complex stabilization, interactome modulation and transporter inhibition, thus enabling challenging therapeutic targets to be druggable. Most known molecular glues were identified serendipitously, such as IMiDs, auxin, and rapamycin. In recent years, more rational strategies were explored with the development of chemical biology and a deep understanding of the interaction between molecular glues and proteins, which led to the rational discovery of several molecular glues. Thus, in this review, we aim to highlight the discovery strategies of molecular glues from three aspects: serendipitous discovery, screening methods and rational design principles. We expect that this review will provide a reasonable reference and insights for the discovery of molecular glues.
分子胶可以特异性地诱导两个或多个蛋白质之间的相互作用，从而调节生物功能，已被证明是药物发现中一种强大的治疗模式。它在几种生物过程中发挥着多种重要作用，如复合物稳定、互作组调节和转运体抑制，从而使具有挑战性的治疗靶点能够成为药物靶点。大多数已知的分子胶都是偶然发现的，如 IMiDs、生长素和雷帕霉素。近年来，随着化学生物学的发展和对分子胶与蛋白质相互作用的深入了解，人们探索了更多合理的策略，从而合理地发现了几种分子胶。因此，在这篇综述中，我们旨在从三个方面强调分子胶的发现策略：偶然发现、筛选方法和合理的设计原则。我们希望这篇综述能为分子胶的发现提供合理的参考和见解。
