As the central figure of the cellular protein degradation machinery, the proteasome is critical for cell survival. Having been extensively targeted for inhibition, the constitutive proteasome has proven its role as a highly valuable drug target. However, recent advances in the protein homeostasis field suggest that additional chapters can be added to this successful story. For example, selective immunoproteasome inhibition promises high clinical efficacy for autoimmune disorders and inflammation, and proteasome inhibitors might serve as novel therapeutics for malaria or other microorganisms. Furthermore, utilizing the destructive force of the proteasome for selective degradation of essential drivers of human disorders has opened up a new and exciting area of drug discovery. Thus, the field of proteasome drug discovery still holds exciting questions to be answered and does not simply end with inhibiting the constitutive proteasome.

中文翻译：

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现代药物发现中的蛋白酶体：高价值药物靶标的第二生命

作为细胞蛋白质降解机制的核心人物，蛋白酶体对于细胞存活至关重要。组成性蛋白酶体已被广泛地抑制，已证明其作为高度有价值的药物靶标的作用。但是，蛋白质稳态领域的最新进展表明，可以将其他章节添加到这个成功的故事中。例如，选择性的免疫蛋白酶体抑制有望对自身免疫性疾病和炎症具有很高的临床疗效，而蛋白酶体抑制剂可作为疟疾或其他微生物的新型治疗剂。此外，利用蛋白酶体的破坏力选择性降解人类疾病的基本驱动因素，开辟了新的令人兴奋的药物发现领域。因此，