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Discovery of benzothiazole derivatives as novel orally receptor-interacting protein kinase 1 (RIPK1) inhibitors for inflammatory disease therapy

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机构: [1]State Key Laboratory of Biotherapy, Cancer Center and Collaborative Innovation Center of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China [2]Chengdu Zenitar Biomedical Technology Co., Ltd., Chengdu, 610041, China [3]Department of Emergency Medicine, Institute of Disaster Medicine, Institute of Emergency Medicine, Disaster Medical Center, West China Hospital of Sichuan University, Chengdu, 610041, China [4]Laboratory of Neuro-System and Multimorbidity, West China Hospital of Sichuan University, Chengdu, 610041, China [5]Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, 610041, China [6]School of Pharmacy/School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
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Receptor-interacting protein kinase 1 (RIPK1), a significant node in the TNF signaling pathway, plays a critical role in modulating inflammatory cell proliferation, apoptosis, and necroptosis. Herein, we report the discovery of benzothiazole derivatives as potent RIPK1 inhibitors. Among them, compound 2q demonstrated significant anti-necroptotic activity by protecting cells against necroptosis. In addition, compound 2q exhibited excellent bioavailability and provided strong protective effects in the systemic inflammatory response syndrome (SIRS) model and humanized acute graft versus host disease (GVHD) model. Collectively, these findings indicate that 2q is a novel and promising candidate for the treatment of inflammatory diseases.Copyright © 2025 Elsevier Masson SAS. All rights reserved.

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大类 | 2 区 医学
小类 | 1 区 药物化学
最新[2025]版:
大类 | 2 区 医学
小类 | 1 区 药物化学
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第一作者机构: [1]State Key Laboratory of Biotherapy, Cancer Center and Collaborative Innovation Center of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China
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通讯机构: [1]State Key Laboratory of Biotherapy, Cancer Center and Collaborative Innovation Center of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China [2]Chengdu Zenitar Biomedical Technology Co., Ltd., Chengdu, 610041, China [*1]State Key Laboratory of Biotherapy, Cancer Center and Collaborative Innovation Center of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China
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