title: Non-covalent proteasome inhibitors.
abstract: Regulator of a vast array of vital cellular processes including cell-cycle progression, apoptosis and antigen presentation, the proteasome represents a major therapeutic target. Therefore, selective inhibitors of the proteasome are promising candidates to develop new treatments for diseases like inflammation, immune diseases and cancer. For proof, the boronic acid, Bortezomib has been approved for treating incurable multiple myeloma in 2003 and mantle lymphoma in 2006 and five others proteasome inhibitors are currently in clinical trials for treatment of different cancers. These compounds and many described proteasome inhibitors interact covalently with the active site of the enzyme through an electrophilic reactive function. Non-covalent inhibitors, mainly peptides, pseudopeptides and some organic compounds, have been less widely investigated. Devoid of reactive function prone to nucleophilic attack, they could offer the advantage of an improved selectivity, a less excessive reactivity and instability which are often associated with side effects in therapeutics. This review highlights the current state of research in the field of non-covalent proteasome inhibitors.
authors.affiliation: Molécules Fluorées et Chimie Médicinale, BioCIS UMR-CNRS 8076, LabEx LERMIT, Universite Paris- Sud, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296, Châtenay- Malabry Cedex, France.
authors.forename: Julia
authors.initials: J
authors.lastname: Kaffy
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bernadat
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ongeri
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010446:Peptide Fragments / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects*; D061988:Proteasome Inhibitors / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D010446:Peptide Fragments; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex