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TARGETED PROTEIN DEGRADATION

Prospecting for molecular glues

Two recent studies identified CDK12 inhibitors that bind to CDK12–cyclin K complexes and act as molecular glues to stabilize an interaction with the ubiquitin ligase CUL4–DDB1, leading to cyclin K degradation.

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Fig. 1: Mechanism of CDK12 inhibitor induced cyclin K degradation by CUL4–DDB1.

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Correspondence to J. Russell Lipford.

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Both authors are employees and shareholders of Amgen.

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den Besten, W., Lipford, J.R. Prospecting for molecular glues. Nat Chem Biol 16, 1157–1158 (2020). https://doi.org/10.1038/s41589-020-0620-z

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