Tipping the balance: synthesis and evaluation of centrinone-based degraders of polo-like kinase 4
Abstract
the ubiquitin-proteasome system. While all synthesized degraders retained low nanomolar binding affinities to the kinase domain of PLK4, large differences were found with respect to their ability to change cellular PLK4 levels. We uncover a complex pharmacological profile of the most potent degraders, D6 and D10, consisting of concomitant lowering of PLK4 levels through degradation, and enhancing PLK4 levels through inhibition of its autoregulation - dependent on its localization at the centrioles.
Fields of Study & Subjects
Protein Degradation and Inhibitors
Chromatin Remodeling and Cancer
Melanoma and MAPK Pathways
Publication details
- Journal / source
- RSC Chemical Biology
- Publisher
- Royal Society of Chemistry (RSC)
- Volume
- 7
- Issue
- 7
- Pages
- 1341–1351
- Publication date
- 1 January 2026
- Language
- EN