title: A small-molecule inhibitor of NF-κB-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury.
abstract: Potent and selective chemical probes are valuable tools for discovery of novel treatments for human diseases. NF-κB-inducing kinase (NIK) is a key trigger in the development of liver injury and fibrosis. Whether inhibition of NIK activity by chemical probes ameliorates liver inflammation and injury is largely unknown. In this study, a small-molecule inhibitor of NIK, B022, was found to be a potent and selective chemical probe for liver inflammation and injury. B022 inhibited the NIK signaling pathway, including NIK-induced p100-to-p52 processing and inflammatory gene expression, both in vitro and in vivo Furthermore, in vivo administration of B022 protected against not only NIK but also CCl4-induced liver inflammation and injury. Our data suggest that inhibition of NIK is a novel strategy for treatment of liver inflammation, oxidative stress, and injury.-Ren, X., Li, X., Jia, L., Chen, D., Hou, H., Rui, L., Zhao, Y., Chen, Z. A small-molecule inhibitor of NF-κB-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury.
authors.affiliation: Key Laboratory of Molecular Epigenetics of the Ministry of Education, School of Life Sciences, Northeast Normal University, Changchun, China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Ren
authors.affiliation: Key Laboratory of Molecular Epigenetics of the Ministry of Education, School of Life Sciences, Northeast Normal University, Changchun, China.
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Epigenetics of the Ministry of Education, School of Life Sciences, Northeast Normal University, Changchun, China.
authors.forename: Linna
authors.initials: L
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Meteria Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Deheng
authors.initials: D
authors.lastname: Chen
authors.affiliation: Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China; and.
authors.forename: Hai
authors.initials: H
authors.lastname: Hou
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Liangyou
authors.initials: L
authors.lastname: Rui
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Meteria Medica, Chinese Academy of Sciences, Shanghai, China; yjzhao@simm.ac.cn.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Molecular Epigenetics of the Ministry of Education, School of Life Sciences, Northeast Normal University, Changchun, China; chenz100@nenu.edu.cn.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D002252:Carbon Tetrachloride Poisoning; D002460:Cell Line; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D006801:Humans; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000067996:RAW 264.7 Cells; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000097782:NF-kappaB-Inducing Kinase
keywords: CCl4; NIK; inflammation; liver injury