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

Yao, Ke; Cho, Yong-Yeon; Bode, Ann M.; Vummenthala, Anuradha; Park, Jewn Giew; Liu, Kangdong; Pang, Yuan-Ping; Dong, Zigang

doi:10.1016/j.febslet.2009.06.017

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Volume 583, Issue 13 , Pages 2208-2212, 7 July 2009

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

Edited by Dietmar J. Manstein

Ke Yao
- The Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States
- These authors contributed equally to this work.
Yong-Yeon Cho
- The Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States
- These authors contributed equally to this work.
Ann M. Bode
- The Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States
Anuradha Vummenthala
- Computer-Aided Molecular Design Laboratory, Mayo Clinic, Rochester, MN, United States
Jewn Giew Park
- Computer-Aided Molecular Design Laboratory, Mayo Clinic, Rochester, MN, United States
Kangdong Liu
- The Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States
Yuan-Ping Pang
- Computer-Aided Molecular Design Laboratory, Mayo Clinic, Rochester, MN, United States
Zigang Dong
- The Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States
- Corresponding author. Fax: +1 507 437 9606.

Received 24 February 2009; received in revised form 1 June 2009; accepted 3 June 2009. published online 15 June 2009.

Abstract

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.