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Updated: Sep 10, 2026

Spatiotemporally Controlled Nuclear Translocation of Guests in Living Cells Using Caged Molecular Glues as Photoactivatable Tags
Published on: January 17, 2019
Covalent warheads as a versatile platform for molecular glue development
Bo Zhang1, Shiji Zhang2, Renshuai Liu2
1Department of Medicinal Chemistry, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shandong Key Laboratory of Druggability Optimization and Evaluation for Lead Compounds, Shandong Basic Science Special Academic Zone (Pharmacy), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University Jinan 250012 China hxb@sdu.edu.cn haofangcn@sdu.edu.cn.
Abstract:
Targeted protein degradation (TPD) has become a novel therapeutic modality for diseases in drug discovery. Most progress on TPD has focused on the ubiquitin proteasome system; however, only a handful of >600 human genome-encoded E3 ligases have been successfully applied. Expansion of the E3 ligase toolbox with novel E3 ligases and their ligands will broaden the potential applications of TPD. Besides that, covalent molecular glue degraders (MGDs) provide a promising direction for TPD. Covalent MGDs may offer several advantages, including increased selectivity, broad applicability to traditionally undruggable proteins, and efficient protein degradation. This review systematically summarizes the latest progress in the field of covalent MGDs, focusing on validated E3 ligases and their corresponding covalent warheads. Structural features, modes of action, and design strategies of covalent MGDs are discussed aiming to provide guidance for the development of novel covalent MGDs.
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