Recent Advances in Targeted Protein Degradation Molecular Glues as Anticancer Drugs

作者：Yulin Shen, Wen Wen, L Chen, Nan Zhang, Cong Wei, Honggang Hu · 发表于：Clinical and Experimental Pharmacology and Physiology · 年份：2025 · DOI：10.1111/1440-1681.70064 · 被引用次数：6 · 研究领域：Protein Degradation and Inhibitors、Ubiquitin and proteasome pathways、Peptidase Inhibition and Analysis

Molecular glues have emerged as a novel class of targeted protein degraders with broad potential in cancer therapy. By inducing proximity between E3 ubiquitin ligases and oncogenic proteins, these agents activate the ubiquitin-proteasome system to drive selective protein degradation. This review systematically explores the application strategies of molecular glues in the targeted degradation of cancer-related proteins located in different subcellular compartments: nuclear cancer proteins (Ikaros, Helios, Aiolos, B-cell lymphoma 6 protein, cyclin K, RNA binding motif protein 39) and cytoplasmic cancer proteins (β-catenin, casein kinase 1α, G1 to S phase transition factor 1). Additionally, this work discusses current challenges and optimisation strategies, offering new perspectives for the development of precision anti-cancer therapeutics.