Targeting JNK for therapeutic benefit: from junk to gold?
The c-Jun NH(2)-terminal kinases (JNKs) phosphorylate and activate members of the activator protein-1 (AP-1) transcription factor family and other cellular factors implicated in regulating altered gene expression, cellular survival and proliferation in response to cytokines and growth factors, noxious stimuli and oncogenic transformation. Because these events are commonly associated with the pathogenesis of a number of human diseases, the potential of JNK inhibitors as therapeutics has attracted considerable interest. Here we discuss the evidence supporting the application of JNK inhibitors in inflammatory, vascular, neurodegenerative, metabolic and oncological diseases in humans, and describe the present status of drug discovery targeting JNK.
Manning
Anthony M
AM
Roche Pharmaceuticals, 3411 Hillview Avenue, Palo Alto, CA 94306, USA. anthony.manning@roche.com
Davis
Roger J
RJ
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000209:etiology; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
D004791:Enzyme Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases