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Molecular Glue Mimics Recurrent Medulloblastoma Mutations in KBTBD4
March 4, 2025
Major Finding: Hotspot KBTBD4 mutations in medulloblastoma mimic the mechanism of action of UM171 in degrading the CoREST corepressor complex.
Concept: UM171 and recurrent KBTBD4 mutations analogously enhance the interaction of KBTBD4 and HDAC1 to promote CoREST degradation.
Impact: This paradigm of chemogenetic convergence may inform the future therapeutic development of molecular glues.
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