Discovery and design of molecular glue enhancers of CDK12–DDB1 interactions for targeted degradation of cyclin K
Pompom Ghosh, Maximilian Schmitz, Thiyagamurthy Pandurangan, Solomon Tadesse, Sean Chin Chan, John W. Mosior, Luxin Sun, Vinayak Palve, Dylan Grassie, K. Anand, Sylvia M. Frydman, William Roush, E. Schönbrunn, Matthias Geyer, Derek R. Duckett, Andrii Monastyrskyi
Abstract
design of molecular glues that transform four different CDK12 scaffold inhibitors, including the clinical pan-CDK inhibitor dinaciclib, into cyclin K degraders. These results not only deepen our understanding of CDK12's role in cell regulation but also underscore significant progress in designing molecular glues for targeted protein degradation in cancers associated with dysregulated cyclin K activity.
Topics & Concepts
EnhancerDegradation (telecommunications)BromodomainChemistryComputer scienceTranscription factorBiochemistryTelecommunicationsAcetylationGeneCancer-related Molecular PathwaysGenetics and Neurodevelopmental DisordersUbiquitin and proteasome pathways