Therapeutic promise of JNK ATP-noncompetitive inhibitors.
Protein kinases are being increasingly targeted in the quest for new therapeutics, and the c-Jun N-terminal kinases (JNKs) are no exception. Protein-kinase inhibitors are generally small molecules that show competitive inhibition with respect to ATP. However, a peptide has been developed that is an ATP-noncompetitive inhibitor of JNK. This article describes the use of this peptide in an increasing number of animal models of disease, including diabetes, stroke, neurotrauma, hearing loss and Alzheimer's disease. The efficacy of this peptide shows that JNK inhibition is an effective strategy for the treatment of these diseases and opens the possibility for testing whether JNK inhibition will be beneficial in other diseases, such as atherosclerosis, arthritis and a range of neurodegenerative diseases.
Bogoyevitch
Marie A
MA
Cell Signalling Laboratory, Biochemistry and Molecular Biology, University of Western Australia, 35 Stirling Highway, Crawley, Western Australia 6009, Australia. marieb@cyllene.uwa.edu.au
D000818:Animals; D001168:Arthritis / Q000188:drug therapy* / Q000378:metabolism; D001667:Binding, Competitive; D004195:Disease Models, Animal; D015195:Drug Design; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
D047428:Protein Kinase Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases