Unlocking the FBOX: Building an End-to-End Discovery engine for Molecular Glues Using a Novel E3 Ligase
- We established an CUL1 E3 ligase not previously exploited for TPD starting from a dedicated DNA encoded library (DEL) screen
- Hit ligands were systematically optimized for physicochemical properties and converted into a focused, glue-like compound library purpose-built for downstream target profiling
- Affinity-enrichment mass spectrometry mapping of glueable targets revealed a target space which is distinct from established ligases such as CRBN