免疫蛋白酶体抑制剂：治疗恶性血液病、自身免疫和炎症性疾病的有前景的策略

Title:Immunoproteasome-Selective Inhibitors: A Promising Strategy to Treat Hematologic Malignancies, Autoimmune and Inflammatory Diseases

Volume: 23 Issue: 12

Author(s): Roberta Ettari, Santo Previti, Alessandra Bitto, Silvana Grasso, Maria Zappalà

Affiliation:

关键词: 免疫蛋白酶体，核心颗粒，免疫蛋白酶体的选择性抑制剂，血液系统恶性肿瘤、自身免疫性疾病、炎症性疾病。

摘要: The immunoproteasome is predominantly expressed in monocytes and lymphocytes and is responsible for the generation of antigenic peptides for cell-mediated immunity. Upon the exposure of inflammatory cytokines IFN-γ and TNF-α, constitutive subunits can be replaced by the synthesis of the immuno-core particles β1i, β2i and β5i. Recent studies demonstrated that the immunoproteasome function is not only limited to MHC class I presentation, but it is also implicated in a number of pathological disorders including hematological malignancies, inflammatory and autoimmune diseases. At present the commercially available proteasome inhibitors Bortezomib and Carfilzomib, which have been validated in multiple myeloma and other diseases, appear to target both the constitutive and immunoproteasomes indiscriminately. This lack of specificity may, in part, explain some of the side effects of these agents. In contrast, by selectively targeting the immunoproteasome, it may be possible to keep the antimyeloma and antilymphoma efficacy unchanged and, at the same time, to increase the therapeutic index. The aim of this review article is to discuss the most promising immunoproteasome core particle-selective inhibitors which have been developed in the recent years, with a particular attention to their structural features, mechanism of action and therapeutic application.

Cite this article as:

Roberta Ettari, Santo Previti, Alessandra Bitto, Silvana Grasso, Maria Zappalà , Immunoproteasome-Selective Inhibitors: A Promising Strategy to Treat Hematologic Malignancies, Autoimmune and Inflammatory Diseases, Current Medicinal Chemistry 2016; 23 (12) . https://dx.doi.org/10.2174/0929867323666160318173706