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    TARGETED PLASMA PROTEIN DEGRADATION
    1.
    发明公开
    TARGETED PLASMA PROTEIN DEGRADATION 审中-公开

    公开(公告)号：US20230398224A1

    公开(公告)日：2023-12-14

    申请号：US17760081

    申请日：2021-02-04

    Applicant: Novartis AG

    Inventor： Martin Allan ,  Jeffrey T. BAGDANOFF ,  David Weninger Barnes ,  Kevin Clairmont ,  Thomas Smith ,  Shuangxi Wang

    IPC: A61K47/54 ,  C07K7/64

    CPC classification number: A61K47/549 ,  C07K7/64

    Abstract: The present invention is directed to the bifunctional compounds and the use of such bifunctional compounds to lower plasma levels of extracellular target molecules by lysosomal degradation. Such bifunctional compounds have a cell surface receptor ligand covalently linked to a ligand that is capable of binding to an extracellular target molecule (such as a ligand for a growth factor, a cytokine, a chemokine, a hormone, a neurotransmitter, a capsid, a soluble receptor, an extracellular secreted protein, an antibody, a lipoprotein, an exosome, a virus, a cell, or a plasma membrane protein), where the cell surface receptor is associated with receptor mediated endocytosis, including asialoglycoprotein receptor (ASGPR) mediated lysosomal degradation and mannose-6-phosphate (M6PR) mediated lysosomal degradation. Pharmaceutical compositions comprising such bifunctional compounds and methods of treating a disease or disorder mediated by an extracellular molecule using such bifunctional compounds are also provided herein.

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