Recent Advances in Targeted Protein Degradation Molecular Glues as Anticancer Drugs

Abstract

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.