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Spatiotemporally Controlled Nuclear Translocation of Guests in Living Cells Using Caged Molecular Glues as Photoactivatable Tags
Published on: January 17, 2019
Exploring nondegrading molecular glues for protein-protein interactions
Sitong Yu1, Lixin Zhou2, Jing Yang3
1Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China; Lingang Laboratory, Shanghai 200031, China.
Abstract:
Protein-protein interactions (PPIs) are central to cellular signaling and represent attractive, yet challenging drug targets. While molecular glue degraders (MGDs) promote target degradation via E3 ligase recruitment, nondegrading molecular glues (MGs) act independently of ubiquitination to stabilize PPIs, enabling modulation of complex assembly, localization, and signaling. In this review, we outline recent progress in nondegrading MGs, highlighting key presenter proteins, such as FKBP12, Cyclophilin A, and 14-3-3, along with emerging case studies beyond these canonical systems. Advances in chemical biology, structural analysis, and computational design are accelerating discovery in this emerging field. Collectively, these insights position nondegrading MGs as a promising therapeutic modality with distinct mechanisms and broad translational potential.
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