Title:Non-Covalent Proteasome Inhibitors
Volume: 19
Issue: 22
Author(s): Julia Kaffy, Guillaume Bernadat and Sandrine Ongeri
Affiliation:
Keywords:
Proteasome, anti-cancer drugs, non-covalent inhibitors, natural peptides, pseudopeptides, small synthetic molecules.
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.
