Drugging the “Undruggable” 💊

🔸 50 new CRBN neosubstrates
🔸 3 bona fide degraders
🔸 MS-proteomic platform expanding druggable proteome

All of this packed in single paper❗ by colleagues from NEOsphere Biotechnologies GmbH, ICR Centre for Protein Degradation and St. Jude Children’s Research Hospital – ALSAC

Additional highlights
✅ Screened 100 CRBN-binders across two cancer cell lines
✅ Identified 50 novel CRBN neosubstrates❗
✅ Developed SJ41564, SJ41813, and SJ46479 that selectively degrade  KDM4B, G3BP2, and vinculin at low nM concentrations and can be used as chemical probes
✅ Integrated degradation and ubiquitination data confirm direct targeting and provides mechanistic insights

Why it matters
✅ Presented platform and workflow proves to be powerful tool for development of molecular glue degraders and expanding the druggable proteom and advancing the field of targeted protein degradation

Which E3 ligase would you assess as next one using this technology❓

Full article: https://www.nature.com/articles/s41467-025-62829-0

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#Proteomics #DrugDiscovery #TPD #MolecularGlues #ChemicalBiology #MGD #MolecularGlueDegraders #TargetedProteinDegradation #CancerResearch