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

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

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12 Scopus citations

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. 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).

Original languageEnglish (US)
Pages (from-to)2208-2212
Number of pages5
JournalFEBS Letters
Volume583
Issue number13
DOIs
StatePublished - Jul 7 2009

Bibliographical note

Funding Information:
This work is supported by a grant from the Minnesota Partnership for Biotechnology and Medical Genomics (L9046001101), The Hormel Foundation, the Mayo Foundation for Medical Education and Research, and the University of Minnesota Supercomputing Institute.

Keywords

  • AV-7
  • Small-molecule inhibitor
  • Sub-G1 accumulation
  • c-Jun N-terminal kinase inhibitor
  • c-Jun phosphorylation

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