PROTAC and Molecular Glue Degraders of the Oncogenic RNA Binding Protein Lin28.

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 glu

SUBMITTER: Kashkush A 

PROVIDER: S-EPMC11904392 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature