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  • Design, synthesis, and evaluation of BCL-2 targeting PROTACs [Elektronski vir]
    Bricelj, Aleša ...
    BCL-2, a member of the BCL-2 protein family, is an antiapoptotic factor that regulates the intrinsic pathway of apoptosis. Due to its aberrant activity, it is frequently implicated in haematopoietic ... cancers and represents an attractive target for the development of therapeutics that antagonize its activity. A selective BCL-2 inhibitor, venetoclax, was approved for treating chronic lymphocytic leukaemia, acute myeloid leukemia, and other hematologic malignancies, validating BCL-2 as an anticancer target. Since then, alternative therapeutic approaches to modulate the activity of BCL-2 have been explored, such as antibody-drug conjugates and proteolysis-targeting chimeras. Despite numerous research groups focusing on developing degraders of BCL-2 family member proteins, selective BCL-2 PROTACs remain elusive, as disclosed compounds only show dual BCL-xL/BCL-2 degradation. Herein, we report our efforts to develop BCL-2 degraders by incorporating two BCL-2 binding moieties into chimeric compounds that aim to hijack one of three E3 ligases: CRBN, VHL, and IAPs. Even though our project did not result in obtaining a potent and selective BCL-2 PROTAC, our research will aid in understanding the narrow chemical space of BCL-2 degraders.
    Vir: Chemistry : a European journal [Elektronski vir]. - ISSN 1521-3765 (Vol. 30, iss. , e202400430, 2024, )
    Vrsta gradiva - e-članek ; neleposlovje za odrasle
    Leto - 2024
    Jezik - angleški
    COBISS.SI-ID - 197511171

    Povezava(-e):

    https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202400430
    DOI

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