Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a key adaptor protein that regulates the NF-κB pathway, in which MALT1 functions as a scaffold protein and protease to trigger downstream signals. The abnormal expression of MALT1 is closely associated with lymphomagenesis and other diseases, including solid tumors and autoimmune diseases. MALT1 is the only protease in the underlying pathogenesis of these diseases, and its proteolytic activity can be pharmacologically regulated. Therefore, MALT1 is a potential and promising target for anti-lymphoma and other MALT1-related disease treatments. Currently, the development of MALT1 inhibitors is still in its early stages. This review presents an overview of MALT1, particularly its X-ray structures and biological functions, and elaborates on the pathogenesis of diseases associated with its dysregulation. We then summarize previously reported MALT1 inhibitors, focusing on their molecular structure, biological activity, structure–activity relationship, and limitations. Finally, we propose future research directions to accelerate the discovery of novel MALT1 inhibitors with clinical applications. Overall, this review provides a comprehensive and systematic overview of MALT1-related research advances and serves as a theoretical basis for drug discovery and research.

中文翻译：

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MALT1 作为治疗淋巴瘤和其他与 MALT1 异常相关的疾病的有希望的靶点

黏膜相关淋巴组织淋巴瘤易位蛋白 1 (MALT1) 是调节 NF-κB 通路的关键衔接蛋白，其中 MALT1 充当支架蛋白和蛋白酶以触发下游信号。MALT1的异常表达与淋巴瘤和其他疾病密切相关，包括实体瘤和自身免疫性疾病。MALT1 是这些疾病潜在发病机制中唯一的蛋白酶，其蛋白水解活性可以通过药理学进行调节。因此，MALT1 是抗淋巴瘤和其他 MALT1 相关疾病治疗的潜在且有前景的靶点。目前，MALT1抑制剂的开发仍处于早期阶段。这篇综述概述了 MALT1，特别是它的 X 射线结构和生物学功能，并详细阐述了与其失调相关的疾病的发病机制。然后我们总结了先前报道的 MALT1 抑制剂，重点是它们的分子结构、生物活性、构效关系和局限性。最后，我们提出了未来的研究方向，以加速发现具有临床应用的新型 MALT1 抑制剂。总体而言，本综述全面系统地概述了 MALT1 相关的研究进展，并为药物发现和研究提供了理论基础。我们提出了未来的研究方向，以加速发现具有临床应用的新型 MALT1 抑制剂。总体而言，本综述全面、系统地概述了 MALT1 相关研究进展，并为药物发现和研究提供了理论基础。我们提出了未来的研究方向，以加速发现具有临床应用的新型 MALT1 抑制剂。总体而言，本综述全面、系统地概述了 MALT1 相关研究进展，并为药物发现和研究提供了理论基础。