Towards the Rational Design of Monovalent Degraders: Lessons Learnt from Cyclin K Degraders.
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Embargo End Date
ICR Authors
Authors
Thomas, KL
Bellenie, BR
Rossanese, OW
Bellenie, BR
Rossanese, OW
Document Type
Journal Article
Date
2025-03-26
Date Accepted
2025-02-13
Abstract
Monovalent degraders can enhance pre-existing surface complementarity between a target protein and a ligase to induce target degradation via the proteasome. For the most part, degraders have been discovered serendipitously and structure-activity relationship (SAR) studies have been limited, making it difficult to rationally design new compounds. Here we discuss how work on the SAR of cyclin K degraders demonstrates that a broad range of compounds can stabilise protein-protein interactions to induce degradation and how it lays the foundation for further monovalent degrader discovery.
Citation
Chimia, 2025, 79 (3), pp. 162 - 166
Source Title
Chimia
Publisher
SWISS CHEMICAL SOC
ISSN
0009-4293
eISSN
2673-2424
Collections
Research Team
Target Eval & Mol Ther
Medicinal Chemistry 4
Directorate Canc Ther
Medicinal Chemistry 4
Directorate Canc Ther