High-throughput ligand diversification to discover chemical inducers of proximity - PubMed
6 days ago
- #protein degradation
- #chemical inducers of proximity
- #high-throughput chemistry
- High-throughput ligand diversification used to discover chemical inducers of proximity (CIPs).
- Sulfur(VI) fluoride exchange-based high-throughput chemistry (HTC) installed 3,163 building blocks on ENL and BRD4 ligands.
- Identified dHTC1, an ENL degrader recruiting CRL4CRBN complex through an extended protein-protein interface.
- Discovered dHTC3, a molecular glue selectively dimerizing BRD4 bromodomain 1 to SCFFBXO3.
- HTC introduced as a tool for discovering new CIPs and effectors for proximity pharmacology.
- Multiple authors have competing interests, including patents, equity, and advisory roles in biotech companies.
- Research funded by various grants from NIH, NSF, and international organizations.