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

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-2 H -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 )