Cereblon molecular glues are widening their reach to protein kinases
- This review covers cereblon-based molecular glue degraders that recruit protein kinases as neosubstrates, extending beyond classic IMiD targets.
- Structures show kinases engaged through varied degron types, such as helical G-loops, an αC-helix glutamate and composite surfaces, explaining selectivity.
- Degradation removes catalytic and non-catalytic functions, which may overcome inhibitor resistance and strengthen combinations.
💡 Points Based on the abstract
Whether glue-induced kinase degrons are structural motifs one can design toward, or quirks of individual scaffolds, is still open. Matched kinase inhibitors and ternary-complex data would help separate true degradation from inhibitor-driven effects. A useful next step is mapping which ligand edits move the exit vector toward the G-loop, then testing how far that logic generalizes across kinases.
Recent discoveries of CRBN-binding molecular glue degraders: Focus on protein kinases ↗