Recent advances in the identification and development of 20S proteasome inhibitors.
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.
García-Echeverría
Carlos
C
Oncology Research, Novartis Pharma Inc., Basel, CH-4002, Switzerland. carlos.garcia-echeverria@pharma.novartis.com
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
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex