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    COMPOUNDS FOR TAU PROTEIN DEGRADATION
    4.
    发明公开
    COMPOUNDS FOR TAU PROTEIN DEGRADATION 审中-公开

    公开(公告)号：EP4310496A2

    公开(公告)日：2024-01-24

    申请号：EP23195169.0

    申请日：2018-07-12

    申请人： Dana-Farber Cancer Institute, Inc. ,  The General Hospital Corporation d/b/a Massachusetts General Hospital

    发明人： GRAY, Nathanael S. ,  HAGGARTY, Stephen J. ,  CAI, Quan ,  TELO BAPTISTA LIMA DA SILVA, Maria Catarina ,  ZHANG, Tinghu ,  FERGUSON, Fleur M.

    IPC分类号： G01N33/534

    摘要： Provided herein are bifunctional compounds that bind tau protein and/or promote targeted ubiquitination for the degradation of tau protein. In particular, provided are compounds that can bind tau protein, a protein whose aggregation is implicated in a variety of neurodegenerative disease (e.g., tauopathies), and can promote its degradation by recruiting an E3 ubiquitin ligase (e.g., Cereblon), which can ubiquitinate tau protein, marking it for proteasomal degradation. Also provided are radiolabeled forms of the bifunctional compounds, pharmaceutical compositions comprising the bifunctional compounds, methods of detecting and/or diagnosing neurological disorders, methods of detecting and/or diagnosing pathological aggregation of tau protein (e.g., in the central nervous system), methods of treating and/or preventing neurological disorders, and methods of promoting the degradation of tau protein by E3 ubiquitin ligase activity in a subject by administering a compound or composition described herein.