Proteasome inhibitors: from research tools to drug candidates.
The 26S proteasome is a 2.4 MDa multifunctional ATP-dependent proteolytic complex, which degrades the majority of cellular polypeptides by an unusual enzyme mechanism. Several groups of proteasome inhibitors have been developed and are now widely used as research tools to study the role of the ubiquitin-proteasome pathway in various cellular processes, and two inhibitors are now in clinical trials for treatment of multiple cancers and stroke.
Kisselev
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AF
Department of Cell Biology, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115, USA. alexei_kisselev@hms.harvard.edu
Goldberg
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AL
D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D001665:Binding Sites; D002384:Catalysis; D006801:Humans; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000737:chemistry* / Q000145:classification / Q000378:metabolism* / Q000627:therapeutic use; D046988:Proteasome Endopeptidase Complex; D020836:Protein Structure, Quaternary; D021122:Protein Subunits; D025801:Ubiquitin / Q000378:metabolism
D019380:Anti-HIV Agents; D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; D021122:Protein Subunits; D025801:Ubiquitin; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease