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Non-Covalent Proteasome Inhibitors

[ Vol. 19 , Issue. 22 ]


Julia Kaffy, Guillaume Bernadat and Sandrine Ongeri   Pages 4115 - 4130 ( 16 )


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.


Proteasome, anti-cancer drugs, non-covalent inhibitors, natural peptides, pseudopeptides, small synthetic molecules.


Molecules Fluorees et Chimie Medicinale, BioCIS UMR-CNRS 8076, LabEx LERMIT, Universite Paris- Sud, Faculte de Pharmacie, 5 rue Jean-Baptiste Clement, 92296, Chatenay- Malabry Cedex, France.

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