A proteomics-first platform screens for molecular glue degraders and identifies a glutathione-activated compound that redirects an E3 ligase to degrade diverse substrates.
Key Takeaways
- M12 functions as a prodrug that is activated through glutathione S -transferase-mediated glutathionylation
- Glutathione moiety binds to an evolutionary conserved glutathione-binding site on DCAF11
- These findings establish that metabolically activated compounds can redirect E3 ligase function