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Xanthatin inhibits STAT3 and NF-kappa B signalling by covalently binding to JAK and IKK kinases

文献类型：期刊论文

作者Liu, Man1,3; Xiao, Cheng-qian2,4; Sun, Ming-wei1,5; Tan, Min-jia1,5; Hu, Li-hong4; Yu, Qiang1,3
刊名JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
出版日期2019-06-01
卷号23期号:6页码:4301-4312
关键词covalent interaction IKK inhibitor JAK inhibitor natural compound
DOI10.1111/jcmm.14322
通讯作者Hu, Li-hong(lhhu@njucm.edu.cn) ; Yu, Qiang(qyu@sibs.ac.cn)
英文摘要Aberrant activation of the signal transducer and activator of transcription 3 (STAT3) and the nuclear factor-kappa B (NF-kappa B) signalling pathways is associated with the development of cancer and inflammatory diseases. JAKs and IKKs are the key regulators in the STAT3 and NF-kappa B signalling respectively. Therefore, the two families of kinases have been the major targets for developing drugs to regulate the two signalling pathways. Here, we report a natural compound xanthatin from the traditional Chinese medicinal herb Xanthium L. as a potent inhibitor of both STAT3 and NF-kappa B signalling pathways. Our data demonstrated that xanthatin was a covalent inhibitor and its activities depended on its alpha-methylene-gamma-butyrolactone group. It preferentially interacted with the Cys243 of JAK2 and the Cys412 and Cys464 of IKK beta to inactivate their activities. In doing so, xanthatin preferentially inhibited the growth of cancer cell lines that have constitutively activated STAT3 and p65. These data suggest that xanthatin may be a promising anticancer and anti-inflammation drug candidate.
WOS关键词STRUCTURAL BASIS ; FERM DOMAIN ; CANCER ; RECEPTOR ; INFLAMMATION ; PHOSPHORYLATION ; ACTIVATION ; PATHWAY ; BETA ; FAMILY
资助项目National Natural Science Foundation of China[81373447] ; National Natural Science Foundation of China[81673465] ; Ministry of Science and Technology of the People's Republic of China[2013CB910900] ; Ministry of Science and Technology of the People's Republic of China[2014ZX9102001002]
WOS研究方向Cell Biology ; Research & Experimental Medicine
语种英语
WOS记录号WOS:000470659500046
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/289670]  
专题新药研究国家重点实验室
通讯作者Hu, Li-hong; Yu, Qiang
作者单位1.Univ Chinese Acad Sci, Beijing, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
4.Nanjing Univ Chinese Med, Jiangsu Key Lab Funct Subst Chinese Med,Sch Pharm, Jiangsu Collaborat Innovat Ctr Chinese Med Resour, Stake Key Lab Cultivat Base TCM Qual & Efficacy, Nanjing, Jiangsu, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Chem Prote Ctr, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Man,Xiao, Cheng-qian,Sun, Ming-wei,et al. Xanthatin inhibits STAT3 and NF-kappa B signalling by covalently binding to JAK and IKK kinases[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2019,23(6):4301-4312.
APA Liu, Man,Xiao, Cheng-qian,Sun, Ming-wei,Tan, Min-jia,Hu, Li-hong,&Yu, Qiang.(2019).Xanthatin inhibits STAT3 and NF-kappa B signalling by covalently binding to JAK and IKK kinases.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,23(6),4301-4312.
MLA Liu, Man,et al."Xanthatin inhibits STAT3 and NF-kappa B signalling by covalently binding to JAK and IKK kinases".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 23.6(2019):4301-4312.

入库方式： OAI收割

来源：上海药物研究所

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