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Igalan attenuates sepsis-induced inflammation through covalent targeting of the NLRP3 inflammasome pathway

Chengchen HouState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaYang ChenState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaWenjie BiKey Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University, Jinan 250012, ChinaLin GaoKey Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University, Jinan 250012, ChinaSimiao YuState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaXiaowen ZhangBeijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, ChinaZekun ChenDepartment of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaTiantian WeiState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaDilnoza DusmatovaInstitute of the Chemistry of Plant Substances, Uzbekistan Academy of Sciences, Tashkent 100170, UzbekistanRimma F МukhamatkhanovaInstitute of the Chemistry of Plant Substances, Uzbekistan Academy of Sciences, Tashkent 100170, UzbekistanIldar D Sham'yanov EInstitute of the Chemistry of Plant Substances, Uzbekistan Academy of Sciences, Tashkent 100170, UzbekistanLiwen HanKey Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University, Jinan 250012, ChinaZhi-Yuan LuKey Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University, Jinan 250012, ChinaHua WangDepartment of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei 230036, ChinaNilufar Z. MamadalievaInstitute of the Chemistry of Plant Substances, Uzbekistan Academy of Sciences, Tashkent 100170, UzbekistanKewu ZengDepartment of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China
RSC Chemical Biologyjournal2026en
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studies demonstrate potent therapeutic effects of Igalan, mitigating systemic inflammation in LPS-challenged zebrafish and providing protection against pulmonary injury and intestinal barrier dysfunction in murine sepsis models. Collectively, our work establishes Igalan as a covalent NLRP3 inhibitor with translational potential for sepsis treatment.

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