Proteasome inhibitors - molecular basis and current perspectives in multiple myeloma.

Abstract

Inhibition of proteasome, a proteolytic complex responsible for the degradation of ubiquitinated proteins, has emerged as a powerful strategy for treatment of multiple myeloma (MM), a plasma cell malignancy. First-in-class agent, bortezomib, has demonstrated great positive therapeutic efficacy in MM, both in pre-clinical and in clinical studies. However, despite its high efficiency, a large proportion of patients do not achieve sufficient clinical response. Therefore, the development of a second-generation of proteasome inhibitors (PIs) with improved pharmacological properties was needed. Recently, several of these new agents have been introduced into clinics including carfilzomib, marizomib and ixazomib. Further, new orally administered second-generation PI oprozomib is being investigated. This review provides an overview of main mechanisms of action of PIs in MM, focusing on the ongoing development and progress of novel anti-proteasome therapeutics.

• Authors: Lenka Kubiczkova, Ludek Pour, Lenka Sedlarikova, Roman Hajek, Sabina Sevcikova
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 18 Issue 6 Pg. 947-61 (Jun 2014) ISSN: 1582-4934 [Electronic] England
• PMID: 24712303 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Proteasome Inhibitors
• Proteasome Endopeptidase Complex

Topics

• Humans
• Multiple Myeloma (drug therapy, enzymology)
• Proteasome Endopeptidase Complex (chemistry)
• Proteasome Inhibitors (therapeutic use)