Proteolysis Targeting Chimera (PROTAC) Linkerology Enhances the CDK-Degradation Selectivity Profile of a Multi-CDK Inhibitor: Discovery of Potent, Anti-Leukemic CDK9 Degraders
The degradation efficiency of a PROTAC─bivalent compounds that link together a ligand for a protein of interest with a ligand for an E3 ligase─is governed, in part, by the length and flexibility of its linker (“linkerology”), as well as the accessibility of ubiquitinatable surface lysines. Based on the prior serendip...