Ru-Yue Zhang, Zi-Xuan Wang, Meng-Yuan Zhang, Yu-Fan Wang, Si-Li Zhou, Jia-Lu Xu, Wen-Xuan Lin, Tian-Rui Ji, Ya-Dong Chen, Tao Lu*, Nian-Guang Li* and Zhi-Hao Shi*,
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MALT1 Inhibitors and Degraders: Strategies for NF-κB-Driven Malignancies
Mucosa-associated lymphoid tissue protein 1 (MALT1), a cysteine protease and the sole paracaspase in humans, plays a pivotal role in the survival and proliferation of NF-κB-dependent malignant cancers, particularly MALT lymphoma and diffuse large B-cell lymphoma (DLBCL). Dysregulated MALT1 activity is implicated in various malignancies, highlighting its importance as a therapeutic target. This Perspective provides an overview of MALT1’s structural and functional characteristics, summarizes recent advancements in small-molecule inhibitors and degraders targeting this protein, and discusses compound structures, structure–activity relationship (SAR) analyses, and biological activities. We aim to inform future research efforts to enhance the activity, selectivity, and pharmacological properties of MALT1-targeting compounds, establishing a foundational framework for drug development in this critical area of cancer therapy.
期刊介绍：
The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents.
The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.
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