Abstract
Small-molecule heterobifunctional degraders can effectively control protein levels and are useful research tools. We assembled proteolysis targeting chimeras (PROTACs) from a cereblon (CRBN) and a von-Hippel-Lindau (VHL) ligase ligand and demonstrated a PROTAC-induced heterodimerization of the two E3 ligases leading to unidirectional and efficient degradation of CRBN.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Cell Line, Tumor
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Cell Survival / drug effects
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Dimerization
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Humans
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Ligands*
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Peptide Hydrolases / chemistry
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Peptide Hydrolases / metabolism
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Proteolysis
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Small Molecule Libraries / chemistry
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Thalidomide / analogs & derivatives
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Thalidomide / chemistry
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Thalidomide / pharmacology
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Ubiquitin-Protein Ligases / chemistry
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Ubiquitin-Protein Ligases / metabolism*
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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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Adaptor Proteins, Signal Transducing
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CRBN protein, human
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Ligands
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Small Molecule Libraries
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Thalidomide
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pomalidomide
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Ubiquitin-Protein Ligases
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Von Hippel-Lindau Tumor Suppressor Protein
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Peptide Hydrolases
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VHL protein, human