title: Recent advances in the identification and development of 20S proteasome inhibitors.
abstract: The involvement of the 20S proteasome in the degradation of critical intracellular regulatory proteins has suggested the potential use of proteasome inhibitors as novel anti-inflammatory agents and for the treatment of cancer and auto-immune diseases. Early inhibitors of the 20S proteasome were relatively non-specific compounds and used for in vitro studies of the ubiquitin/proteasome-dependent degradation pathway. The inherent drawbacks of these inhibitors (e.g., non-target specific, too reactive or unstable) has prompted medicinal chemists to search for alternative subunit-specific proteasome inhibitors. This manuscript summarises recent salient medicinal chemistry achievements in this area of research.
authors.affiliation: Oncology Research, Novartis Pharma Inc., Basel, CH-4002, Switzerland. carlos.garcia-echeverria@pharma.novartis.com
authors.forename: Carlos
authors.initials: C
authors.lastname: García-Echeverría
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000502:physiology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000502:physiology; D046988:Proteasome Endopeptidase Complex; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex