Development of a molecular glue-based Lin28 degrader to regulate cellular proliferation and stemness.

Let-7 microRNAs (miRNAs) regulate cellular processes including stemness and proliferation. Lin28, an RNA-binding protein, controls let-7 miRNA biogenesis and is a key factor in maintaining stem cell properties. We developed SB1349, a novel molecular glue-based degrader targeting Lin28. SB1349 induces Lin28 degradation through a proteasome-dependent pathway, enhances let-7 miRNA levels, and downregulates oncogenes c-Myc and IMP1. SB1349 also promotes the differentiation in neuroblastoma cells, highlighting its potential as a therapeutic agent for various diseases.

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Minha Lee, Wan Gi Byun, Sumin Son, Seung Bum Park. Development of a molecular glue-based Lin28 degrader to regulate cellular proliferation and stemness. Chemical communications (Cambridge, England). 2024 Oct 24;60(86):12525-12528

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PMID: 39324213

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