Property-Based Optimization of Cereblon-Based Molecular Glue Degraders

Molecular glue degraders that bind the E3 ligase adaptor cereblon are clinically precedented drugs used to treat cancer. Highly potent next-generation degraders are in development that target difficult-to-drug neosubstrates, such as transcription factors, for several different indications. This Microperspective covers the medicinal chemistry strategies being used to advance the property-based optimization of cereblon-based molecular glue degraders through consideration of their physicochemical characteristics.