Expanding the targeted protein degradation approach with small molecule chimeras directed to the 26S proteasome - PubMed
3 hours ago
- #USP14
- #26S proteasome
- #targeted protein degradation
- Classical PROTACs bind specific targets and E3 ubiquitin ligases to promote ubiquitination and degradation via the proteasome.
- Alternative targeted protein degradation strategies are being explored due to limitations of E3-based PROTACs.
- Proof of concept is provided for 26S-oriented compounds using small-molecule ligands of USP14, a 26S-associated deubiquitinase.
- Models used include oncology-relevant targets IMPDH2 and CERT1 to demonstrate this approach.
- The findings expand the potential of targeted protein degradation beyond traditional E3 ligase-based methods.