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The New Frontier: Merging Molecular Glue Degrader and Antibody–Drug Conjugate Modalities To Overcome Strategic Challenges

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    The New Frontier: Merging Molecular Glue Degrader and Antibody–Drug Conjugate Modalities To Overcome Strategic Challenges
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    Journal of Medicinal Chemistry

    Cite this: J. Med. Chem. 2024, XXXX, XXX, XXX-XXX
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    https://doi.org/10.1021/acs.jmedchem.4c01289
    Published September 4, 2024
    © 2024 American Chemical Society
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    Herein, we discuss advancements in the field of a unique class of antibody–drug conjugates (ADCs) named molecular glue–antibody conjugate (MAC). ADCs traditionally employ cytotoxic agents as payloads, and this approach has been used in all approved ADCs to treat cancer. Complementary to this approach, proteolysis targeting chimera (PROTAC) degrader antibody conjugates (DACs) provide a unique opportunity to deliver these bifunctional agents to tumors by using antibodies as a delivery mechanism to overcome the bioavailability issues encountered by PROTAC payloads. Recently, a cereblon binding monovalent degrader called molecular glues has been used in new ADCs that we have coined the term molecular–glue antibody conjugates (MACs). In this article, we intend to review advancements made in the field of targeted delivery of cereblon-based molecular glue degraders.

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    Journal of Medicinal Chemistry

    Cite this: J. Med. Chem. 2024, XXXX, XXX, XXX-XXX
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jmedchem.4c01289
    Published September 4, 2024
    © 2024 American Chemical Society
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