The proteasome: a new target for novel drug therapies.

Abstract	The proteasome is an enzyme present in all cells, from yeast to human, and has a central role in the proteolytic degradation of the vast majority of intracellular proteins. Among the key proteins modulated by the proteasome are those involved in controlling inflammatory processes, cell cycle regulation, and gene expression. As such, agents that inhibit the proteasome have been shown to be active in numerous animal models of inflammation and cancer Two proteasome inhibitors are under clinical evaluation. PS-519 is being studied for the treatment of reperfusion injury that occurs following cerebral ischemia and myocardial infarction. The other, PS-341, has recently entered multiple phase 2 clinical trials for the treatment of multiple myeloma, chronic lymphocytic leukemia, and a variety of solid tumors. The proteasome may have an important role in the evolution of HIV-related disorders including AIDS and inflammatory disorders. Therapeutic strategies using proteasome inhibitors for the treatment of these conditions have now entered preclinical development.
Authors	P J Elliott, J S Ross
Journal	American journal of clinical pathology (Am J Clin Pathol) Vol. 116 Issue 5 Pg. 637-46 (Nov 2001) ISSN: 0002-9173 [Print] England
PMID	11710679 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Review)
Chemical References	Antineoplastic Agents Boronic Acids Cysteine Proteinase Inhibitors Multienzyme Complexes PS519 Pyrazines Bortezomib Cysteine Endopeptidases Proteasome Endopeptidase Complex Acetylcysteine
Topics	Acetylcysteine (analogs & derivatives, pharmacokinetics, therapeutic use) Animals Antineoplastic Agents (pharmacokinetics, therapeutic use) Boronic Acids (pharmacokinetics, therapeutic use) Bortezomib Carcinoma, Lewis Lung (drug therapy, enzymology) Clinical Trials, Phase I as Topic Cysteine Endopeptidases Cysteine Proteinase Inhibitors (pharmacokinetics, therapeutic use) Disease Models, Animal Humans Multienzyme Complexes (antagonists & inhibitors) Neoplasms (drug therapy, enzymology) Proteasome Endopeptidase Complex Pyrazines (pharmacokinetics, therapeutic use)

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