ArticleMacromolecular bioscience2025
PROTAC and Molecular Glue Degraders of the Oncogenic RNA Binding Protein Lin28.
Article in Macromolecular bioscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Review
- Review
- The Hallmarks of Glioblastoma: Functional Interplay Between Long Non-Coding RNAs and RNA-Binding Proteins.Cells · 2026Review
- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Modulation of the tumor microenvironment by the ubiquitin-proteasome system in colorectal cancer.Journal of translational medicine · 2025Review
- Development of PROTAC-Based Strategies for Cannabinoid Receptor Type 1 (CBACS pharmacology & translational science · 2025Article
- Article
- PROTAC and Molecular Glue Degraders of the Oncogenic RNA Binding Protein Lin28.Macromolecular bioscience · 2025Article
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Authors and funding
4 authors.
Funding
Abstract
The interaction between proteins and RNA is crucial for regulating gene expression, with dysregulation often linked to diseases such as cancer. The RNA-binding protein (RBP) Lin28 inhibits the tumor suppressor microRNA (miRNA) let-7, making it a significant oncogenic factor in tumor progression and metastasis. In this study, a small molecule is used that binds Lin28 and blocks its inhibition of let-7. To enhance its efficay, the inhibitor is transformed into degraders via two degradation approaches: Proteolysis Targeting Chimera (PROTAC) and molecular glue. A series of PROTAC bifunctional molecules and molecular glues capable of degrading Lin28 in cells.is developed Both strategies significantly reduce overexpressed Lin28 and alleviate cancer cellular phenotypes. Notably, the molecular glue approach demonstrates exceptional potency, surpassing PROTAC in several aspects. This outcome underscores the superior efficiency of the molecular glue approach for targeted Lin28 degradation and highlights its potential for addressing associated diseases with small molecules. Innovative small molecule strategies such as molecular glue and PROTAC technology for targeted RBP degradation, hold promise for opening new avenues in RNA modulation and addressing related diseases.
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