Abstract
E3 ubiquitin ligases, such as the therapeutically relevant VHL, are challenging targets for traditional medicinal chemistry, as their modulation requires targeting protein-protein interactions. We report novel small-molecule inhibitors of the interaction between VHL and its molecular target HIF1α, a transcription factor involved in oxygen sensing.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Crystallography, X-Ray
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Drug Design
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology*
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
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Inhibitory Concentration 50
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Models, Molecular
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Protein Interaction Maps / drug effects*
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Von Hippel-Lindau Tumor Suppressor Protein / antagonists & inhibitors*
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Von Hippel-Lindau Tumor Suppressor Protein / chemistry
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Von Hippel-Lindau Tumor Suppressor Protein / metabolism*
Substances
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Enzyme Inhibitors
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Hypoxia-Inducible Factor 1, alpha Subunit
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Von Hippel-Lindau Tumor Suppressor Protein
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VHL protein, human