Projects per year
E3 ubiquitin ligases are attractive targets in the ubiquitin-proteasome system, however, the development of small-molecule ligands has been rewarded with limited success. The von Hippel-Lindau protein (pVHL) is the substrate recognition subunit of the VHL E3 ligase that targets HIF-1α for degradation. We recently reported inhibitors of the pVHL:HIF-1α interaction, however they exhibited moderate potency. Herein, we report the design and optimization, guided by X-ray crystal structures, of a ligand series with nanomolar binding affinities.
- Crystallography, X-Ray
- Hypoxia-Inducible Factor 1, alpha Subunit
- Models, Molecular
- Molecular Targeted Therapy
- Protein Binding
- Small Molecule Libraries
- Structure-Activity Relationship
- Von Hippel-Lindau Tumor Suppressor Protein
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
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