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

FEBS Lett. 2009 Jul 7;583(13):2208-12. doi: 10.1016/j.febslet.2009.06.017. Epub 2009 Jun 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / chemistry*
  • Animals
  • Cells, Cultured
  • Embryo, Mammalian / metabolism
  • Humans
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase 10 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 10 / genetics
  • Mitogen-Activated Protein Kinase 10 / metabolism
  • Mitogen-Activated Protein Kinase 8 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 8 / genetics
  • Mitogen-Activated Protein Kinase 8 / metabolism
  • Mitogen-Activated Protein Kinase 9 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 9 / genetics
  • Mitogen-Activated Protein Kinase 9 / metabolism
  • Phosphorylation
  • Protein Kinase Inhibitors / chemistry*
  • Pyrazoles / chemistry*
  • Ultraviolet Rays

Substances

  • 7-(6-N-phenylaminohexyl)amino-2H-anthra(1,9-cd)pyrazol-6-one
  • Aniline Compounds
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Mitogen-Activated Protein Kinase 10
  • Mitogen-Activated Protein Kinase 9
  • Mitogen-Activated Protein Kinase 8