title: 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-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.
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Yao
authors.forename: Yong-Yeon
authors.initials: YY
authors.lastname: Cho
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Anuradha
authors.initials: A
authors.lastname: Vummenthala
authors.forename: Jewn Giew
authors.initials: JG
authors.lastname: Park
authors.forename: Kangdong
authors.initials: K
authors.lastname: Liu
authors.forename: Yuan-Ping
authors.initials: YP
authors.lastname: Pang
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry*; D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D048057:Mitogen-Activated Protein Kinase 10 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D011720:Pyrazoles / Q000737:chemistry*; D014466:Ultraviolet Rays
chemical_list: C543321:7-(6-N-phenylaminohexyl)amino-2H-anthra(1,9-cd)pyrazol-6-one; D000814:Aniline Compounds; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D048057:Mitogen-Activated Protein Kinase 10; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8