Degradation by Design: New Cyclin K Degraders from Old CDK Inhibitors.

ABSTRACT: Small molecules that induce protein degradation hold the potential to overcome several limitations of the currently available inhibitors. Monovalent or molecular glue degraders, in particular, enable the benefits of protein degradation without the disadvantages of high molecular weight and the resulting challenge in drug development that are associated with bivalent molecules like Proteolysis Targeting Chimeras. One key challenge in designing monovalent degraders is how to build in the degrader activity─how can we convert an inhibitor into a degrader? If degradation activity requires very specific molecular features, it will be difficult to find new degraders and challenging to optimize those degraders toward drugs. Herein, we demonstrate that an unexpectedly wide range of modifications to

SUBMITTER: Thomas KL 

PROVIDER: S-EPMC10804372 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature