Abstract
Because of the encouraging results obtained using vinyl ester derivatives, we synthesized and tested a novel series of peptide-based proteasome inhibitors bearing a new pharmacophore unit at the C-terminal. N-Acylpyrrole moiety is a potential substrate for Michael addition by catalytic threonine. Several analogues have demonstrated a selective inhibition of the multicatalytic complex beta1 subunits, the capacity to permeate cellular membrane, and good pharmacokinetics properties.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Catalytic Domain
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Cell Line, Tumor
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Cell Membrane Permeability
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Drug Screening Assays, Antitumor
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Drug Stability
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Humans
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Models, Molecular
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Oligopeptides / chemical synthesis*
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Oligopeptides / pharmacokinetics
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Oligopeptides / pharmacology
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Proteasome Endopeptidase Complex / blood
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Proteasome Endopeptidase Complex / chemistry
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Proteasome Inhibitors*
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Protein Subunits / antagonists & inhibitors
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Pyrroles / chemical synthesis*
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Pyrroles / pharmacokinetics
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Pyrroles / pharmacology
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Structure-Activity Relationship
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Vinyl Compounds / chemical synthesis*
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Vinyl Compounds / pharmacokinetics
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Vinyl Compounds / pharmacology
Substances
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Antineoplastic Agents
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Oligopeptides
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Proteasome Inhibitors
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Protein Subunits
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Pyrroles
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Vinyl Compounds
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Proteasome Endopeptidase Complex