2. Academic Validation
  3. Harnessing the FBXW7 somatic mutant R465C for targeted protein degradation

Harnessing the FBXW7 somatic mutant R465C for targeted protein degradation

  • bioRxiv. 2024 Dec 4:2024.12.03.626601. doi: 10.1101/2024.12.03.626601.
Ananya A Basu 1 2,  Chenlu Zhang 1,  Milad Rouhimoghadam 3,  Anil Vasudevan 3,  Justin M Reitsma 3,  Xiaoyu Zhang 1 2 4 5 6
Affiliations

Affiliations

  • 1 Department of Chemistry, Northwestern University, Evanston, IL 60208.
  • 2 Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208.
  • 3 Technology & Therapeutic Platforms, AbbVie Incorporated, North Chicago, IL 60064.
  • 4 Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611.
  • 5 Center for Human Immunobiology, Northwestern University, Chicago, IL 60611.
  • 6 International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208.
PMID: 39677626 DOI: 10.1101/2024.12.03.626601
Abstract

Targeted protein degradation (TPD) is a pharmacological strategy that eliminates specific proteins from cells by harnessing cellular proteolytic degradation machinery. In proteasome-dependent TPD, expanding the repertoire of E3 Ligases compatible with this approach could enhance the applicability of this strategy across various biological contexts. In this study, we discovered that a somatic mutant of FBXW7, R465C, can be exploited by heterobifunctional compounds for targeted protein degradation. This work demonstrates the potential of utilizing mutant E3 Ligases that occur exclusively in diseased cells for TPD applications.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
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  • HY-173082
    PROTAC FKBP12 Degrader