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Chemoproteomics of Marine Natural Product Naamidine J Unveils CSE1L as a Therapeutic Target in Acute Lung Injury

文献类型：期刊论文

作者Gao, Cheng-Long4,5,6; Song, Jin-Qian6; Yang, Ze-Nan3,4,5; Wang, Haojie2; Wu, Xin-Yuan6; Shao, Changwei4; Dai, Hong-Xia4; Chen, Kaixian5; Guo, Yue-Wei1,4; Pang, Tao6
刊名JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
出版日期2024-09-26
页码14
ISSN号0002-7863
DOI10.1021/jacs.4c09695
通讯作者Guo, Yue-Wei(ywguo@simm.ac.cn) ; Pang, Tao(tpang@cpu.edu.cn) ; Li, Xu-Wen(xwli@simm.ac.cn)
英文摘要Acute lung injury is a devastating illness characterized by severe inflammation mediated by aberrant activation of macrophages, resulting in significant morbidity and mortality, highlighting the urgent need for novel pharmacological targets and drug candidates. In this study, we identified a novel target for regulating inflammation in macrophages and acute lung injury via chemical proteomics and genetics based on a marine alkaloid, naamidine J (NJ). The structures of NJ-related naamidine alkaloids were first confirmed or revised by a combination of quantum chemical calculations and X-ray diffraction analysis. NJ was found as a potential anti-inflammatory agent by screening our compound library, and CSE1L was identified by chemoproteomics as a main cellular target of NJ to inhibit inflammation in macrophages and protect against acute lung injury. Mechanistically, we demonstrated that NJ directly interacted with CSE1L on the sites of His745 and Phe903 and then inhibited the nuclear translocation and transcriptional activity of transcription factor SP1, thereby suppressing inflammation in macrophages and ameliorating acute lung injury. Taken together, these findings have uncovered a novel pharmacological target for the treatment of acute lung injury and have also provided a potential druggable pocket of CSE1L and a lead compound or an available chemical tool from marine sources for investigating CSE1L function and developing novel drug candidates against acute lung injury.
WOS关键词AGENTS
资助项目National Key Research and Development Program of China[2021YFF0502400] ; National Key Research and Development Program of China[2022YFC2804100] ; National Natural Science Foundation of China[82304373] ; National Natural Science Foundation of China[42076099] ; National Natural Science Foundation of China[82174010] ; National Natural Science Foundation of China[81973512] ; National Natural Science Foundation of China[81991521] ; China Postdoctoral Science Foundation[2023M743656] ; Shandong Laboratory Program[SYS202205] ; Taishan Scholars Program[tsqn202312302] ; Fundamental Research Projects of Science & Technology Innovation and development Plan in Yantai City[2023JCYJ057] ; State Key Laboratory of Natural Medicines of China Pharmaceutical University[SKLNMKF202405] ; Double First-Class Project of China Pharmaceutical University[CPUQNJC22_02] ; CAS Youth Interdisciplinary Team and Shanghai Super Postdoc Incentive Program[2022683]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:001324305300001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/313666]  
专题中国科学院上海药物研究所
通讯作者Guo, Yue-Wei; Pang, Tao; Li, Xu-Wen
作者单位1.Shanghai Univ, Sch Med, Shanghai 200444, Peoples R China
2.Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Materia Med, Drug Discovery & Design Ctr, State Key Lab Chem Biol, Shanghai 201203, Peoples R China
6.China Pharmaceut Univ, New Drug Screening & Pharmacodynam Evaluat Ctr, State Key Lab Nat Med, Nanjing 210009, Peoples R China
推荐引用方式
GB/T 7714		 Gao, Cheng-Long,Song, Jin-Qian,Yang, Ze-Nan,et al. Chemoproteomics of Marine Natural Product Naamidine J Unveils CSE1L as a Therapeutic Target in Acute Lung Injury[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2024:14.
APA Gao, Cheng-Long.,Song, Jin-Qian.,Yang, Ze-Nan.,Wang, Haojie.,Wu, Xin-Yuan.,...&Li, Xu-Wen.(2024).Chemoproteomics of Marine Natural Product Naamidine J Unveils CSE1L as a Therapeutic Target in Acute Lung Injury.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,14.
MLA Gao, Cheng-Long,et al."Chemoproteomics of Marine Natural Product Naamidine J Unveils CSE1L as a Therapeutic Target in Acute Lung Injury".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2024):14.

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来源：上海药物研究所

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