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

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.