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.
Keywords: Cyclin K; Monovalent degraders; Targeted protein degradation.
Copyright 2025 Katie L. Thomas, Benjamin R. Bellenie, Olivia W. Rossanese. License: This work is licensed under a Creative Commons Attribution 4.0 International License.