Abstract
The ubiquitin-proteasome system (UPS) pervades the biology of eukaryotes. Because it depends on the activity of hundreds of different enzymes and protein-protein interactions, the UPS provides many opportunities for selective modulation of the pathway with small molecules. Here we discuss the principles that underlie the development of effective inhibitors or activators of the pathway. We emphasize insights from structural analysis and describe strategies for evaluating the selectivity of compounds.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Humans
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Models, Molecular
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Proteasome Endopeptidase Complex / chemistry
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Proteasome Endopeptidase Complex / metabolism*
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Protein Binding / drug effects
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Proteome / drug effects*
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Proteome / metabolism*
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Small Molecule Libraries / chemistry
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Small Molecule Libraries / pharmacology*
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Substrate Specificity / drug effects
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Ubiquitin / antagonists & inhibitors
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Ubiquitin / chemistry
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Ubiquitin / metabolism*
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Ubiquitin-Conjugating Enzymes / chemistry
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Ubiquitin-Conjugating Enzymes / metabolism
Substances
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Proteome
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Small Molecule Libraries
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Ubiquitin
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Ubiquitin-Conjugating Enzymes
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Proteasome Endopeptidase Complex