Dana-Farber researchers unveiled a platform for systematically discovering molecular glue degraders, aiming to broaden the therapeutic space beyond the small subset of E3 ligases currently used in clinical degraders. The work describes an approach that screens molecular glue candidates in a scalable workflow and enabled identification of the first metabolically activated molecular glue degrader. The discovery, published in Nature, builds on earlier molecular glue concepts that helped drive drugs such as lenalidomide, but focuses on increasing the diversity of E3 ligases that can be leveraged. The platform is positioned as a discovery engine that could speed degraders targeting proteins previously treated as “undruggable,” especially where binding-site inhibitors have limited traction.