title: Development of proteasome inhibitors as research tools and cancer drugs.
abstract: The proteasome is the primary site for protein degradation in mammalian cells, and proteasome inhibitors have been invaluable tools in clarifying its cellular functions. The anticancer agent bortezomib inhibits the major peptidase sites in the proteasome's 20S core particle. It is a "blockbuster drug" that has led to dramatic improvements in the treatment of multiple myeloma, a cancer of plasma cells. The development of proteasome inhibitors illustrates the unpredictability, frustrations, and potential rewards of drug development but also emphasizes the dependence of medical advances on basic biological research.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. alfred_goldberg@hms.harvard.edu
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Goldberg
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D035843:Biomedical Research / Q000379:methods*; D003585:Cell Biology; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects* / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D061988:Proteasome Inhibitors; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex