Open AccessProteasome inhibitors – molecular basis and current perspectives in multiple myeloma
Author(s) -
Kubiczkova Lenka,
Pour Ludek,
Sedlarikova Lenka,
Hajek Roman,
Sevcikova Sabina
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12279
Subject(s) - carfilzomib , ixazomib , proteasome , bortezomib , multiple myeloma , proteasome inhibitor , medicine , malignancy , ubiquitin , cancer research , pharmacology , bioinformatics , biology , immunology , microbiology and biotechnology , biochemistry , gene
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 ( PI s) 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 PI s in MM , focusing on the ongoing development and progress of novel anti‐proteasome therapeutics.