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

页码：2208 / 2212

页数：5

共 21 条

[1]

Bost F, 1999, MOL CELL BIOL, V19, P1938

[2] The JUN kinase stress-activated protein kinase pathway is required for epidermal growth factor stimulation of growth of human A549 lung carcinoma cells [J].