A selective small-molecule inhibitor of c-Jun N-terminal kinase 1

被引：16
|
作者：
Yao, Ke [1 ]
Cho, Yong-Yeon [1 ]
Bode, Ann M. [1 ]
Vummenthala, Anuradha [2 ]
Park, Jewn Giew [2 ]
Liu, Kangdong [1 ]
Pang, Yuan-Ping [2 ]
Dong, Zigang [1 ]
机构：
[1] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA
[2] Mayo Clin, Comp Aided Mol Design Lab, Rochester, MN USA
来源：
FEBS LETTERS | 2009年 / 583卷 / 13期
关键词：
AV-7; Small-molecule inhibitor; c-Jun N-terminal kinase inhibitor; c-Jun phosphorylation; Sub-G1; accumulation; SIGNAL-TRANSDUCTION PATHWAY; LUNG-CARCINOMA CELLS; INSULIN-RESISTANCE; JNK; TRANSFORMATION; ACTIVATION; GROWTH; SUPPRESSION; APOPTOSIS; OBESITY;
D O I：
10.1016/j.febslet.2009.06.017
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Indiscriminately suppressing total c-Jun N-terminal kinase (JNK) activity is not an appropriate strategy because each JNK appears to have a distinct function in cancer, asthma, diabetes, or Parkinson's disease. Herein, we report that 7-(6-N-phenylaminohexyl) amino-2H-anthra[1,9-cd] pyrazol-6-one (AV-7) inhibited JNK1 activity, but not JNK2 or JNK3. We found that ultraviolet B (UVB) induced c-Jun phosphorylation and sub-G1 accumulation in JNK2 (/) murine embryonic fibroblasts, which contain an abundance of JNK1, but not JNK2. These results demonstrate that AV-7 is an isoform selective small-molecule inhibitor of JNK1 activity, which might be developed as a therapeutic against diabetes. Structured summary: MINT-7148332: JNK3 (uniprotkb: P53779) phosphorylates (MI: 0217) c-JUN (uniprotkb: P05412) by protein kinase assay (MI: 0424) MINT-7148323: JNK2 (uniprotkb: P45984) phosphorylates (MI: 0217) c-JUN (uniprotkb: P05412) by protein kinase assay (MI: 0424) MINT-7148314: JNK1 (uniprotkb: P45983) phosphorylates (MI: 0217) c-JUN (uniprotkb: P05412) by protein kinase assay (MI: 0424) (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
引用
收藏
页码：2208 / 2212
页数：5
相关论文
共 50 条
  • [11] c-Jun N-terminal kinase - c-Jun pathway transactivates Bim to promote osteoarthritis
    Ye, Zhiqiang
    Chen, Yuxian
    Zhang, Rongkai
    Dai, Haitao
    Zeng, Chun
    Zeng, Hua
    Feng, Hui
    Du, Gengheng
    Fang, Hang
    Cai, Daozhang
    CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 2014, 92 (02) : 132 - 139
  • [12] Relationship Between c-Jun N-terminal Kinase and Depression
    Ma, Hongpeng
    2020 INTERNATIONAL CONFERENCE ON ENERGY, ENVIRONMENT AND BIOENGINEERING (ICEEB 2020), 2020, 185
  • [13] The c-Jun N-terminal kinase inhibitor SP600125 is neuroprotective in amygdala kindled rats
    Chen, Xu
    Wu, Jun
    Hua, Dong
    Shu, Kai
    Wang, Jian-Zhi
    Li, Ling
    Lei, Ting
    BRAIN RESEARCH, 2010, 1357 : 104 - 114
  • [14] HEPATIC APOPTOSIS POSTBURN IS MEDIATED BY C-JUN N-TERMINAL KINASE 2
    Marshall, Alexandra H.
    Brooks, Natasha C.
    Hiyama, Yaeko
    Qa'aty, Nour
    Al-Mousawi, Ahmed
    Finnerty, Celeste C.
    Jeschke, Marc G.
    SHOCK, 2013, 39 (02): : 183 - 188
  • [15] c-Jun N-terminal kinase signaling in aging
    Li, Yihao
    You, Li
    Nepovimova, Eugenie
    Adam, Vojtech
    Heger, Zbynek
    Jomova, Klaudia
    Valko, Marian
    Wu, Qinghua
    Kuca, Kamil
    FRONTIERS IN AGING NEUROSCIENCE, 2024, 16
  • [16] Discovery of a selective and potent inhibitor of c-Jun N-terminal kinase 1 with anti-pulmonary fibrosis effect
    Ren, Shuhua
    Liu, Fengling
    Chi, Man
    Liu, Jinfeng
    Huang, Yi
    Huang, Weiwei
    Gu, Wenjing
    Yuan, Yaxia
    Hou, Shurong
    Chen, Xiabin
    Ma, Lei
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2025, 116
  • [17] c-Jun N-terminal kinase/c-Jun inhibits fibroblast proliferation by negatively regulating the levels of stathmin/oncoprotein 18
    Yeap, Yvonne Y. C.
    Ng, Ivan H. W.
    Badrian, Bahareh
    Nguyen, Tuong-Vi
    Yip, Yan Y.
    Dhillon, Amardeep S.
    Mutsaers, Steven E.
    Silke, John
    Bogoyevitch, Marie A.
    Ng, Dominic C. H.
    BIOCHEMICAL JOURNAL, 2010, 430 : 345 - 354
  • [18] The Roles of c-Jun N-Terminal Kinase (JNK) in Infectious Diseases
    Chen, Jing
    Ye, Chao
    Wan, Chao
    Li, Gang
    Peng, Lianci
    Peng, Yuanyi
    Fang, Rendong
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (17)
  • [19] Role of c-Jun N-terminal Kinase in the Regulation of Vascular Tone
    Zhou, Ming-Sheng
    Schulman, Ivonne Hernandez
    Chadipiralla, Kiranmai
    Raij, Leopoldo
    JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS, 2010, 15 (01) : 78 - 83
  • [20] C-Jun N-terminal kinase signalling pathway in response to cisplatin
    Yan, Dong
    An, GuangYu
    Kuo, Macus Tien
    JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2016, 20 (11) : 2013 - 2019
12345