TY - JOUR
T1 - A selective small-molecule inhibitor of c-Jun N-terminal kinase 1
AU - Yao, Ke
AU - Cho, Yong Yeon
AU - Bode, Ann M.
AU - Vummenthala, Anuradha
AU - Park, Jewn Giew
AU - Liu, Kangdong
AU - Pang, Yuan Ping
AU - Dong, Zigang
N1 - 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.
PY - 2009/7/7
Y1 - 2009/7/7
N2 - 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).
AB - 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).
KW - AV-7
KW - Small-molecule inhibitor
KW - Sub-G1 accumulation
KW - c-Jun N-terminal kinase inhibitor
KW - c-Jun phosphorylation
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U2 - 10.1016/j.febslet.2009.06.017
DO - 10.1016/j.febslet.2009.06.017
M3 - Article
C2 - 19527717
AN - SCOPUS:67649311246
SN - 0014-5793
VL - 583
SP - 2208
EP - 2212
JO - FEBS Letters
JF - FEBS Letters
IS - 13
ER -