蛋白酶体调节细胞内过程，维持生物体内稳态，在各种疾病的研究中显示了巨大的意义，如神经退行性疾病、免疫相关疾病和癌症，特别是在多发性骨髓瘤（MM）和幔细胞淋巴瘤（MCL）等造血恶性肿瘤方面。所有临床使用的蛋白酶体抑制剂都结合到蛋白酶体的活性位点上，因此展现出竞争机制。治疗期间产生的耐药和不耐受性推动了对具有不同作用机制的抑制剂的寻求。在本综述中，我们提供了非竞争性蛋白酶体抑制剂的概述，包括它们的作用机制、功能、可能的应用和与竞争性抑制剂相比的优缺点。版权所有 ©2023 Elsevier Inc。保留所有权利。

The proteasome regulates intracellular processes, maintains biological homeostasis, and has shown great significance in the study of various diseases, such as neurodegenerative diseases, immune-related diseases, and cancer, especially in hematologic malignancies such as multiple myeloma (MM) and mantle cell lymphoma (MCL). All clinically used proteasome inhibitors bind to the active site of the proteasome and thus exhibit a competitive mechanism. The development of resistance and intolerance during treatment drives the search for inhibitors with different mechanisms of action. In this review, we provide an overview of noncompetitive proteasome inhibitors, including their mechanisms of action, function, possible applications, and their advantages and disadvantages compared with competitive inhibitors.Copyright © 2023 Elsevier Inc. All rights reserved.