Therapeutic promise of JNK ATP-noncompetitive inhibitors

被引:47
作者
Bogoyevitch, MA [1 ]
机构
[1] Univ Western Australia, Cell Signaling Lab, Crawley, WA 6009, Australia
关键词
D O I
10.1016/j.molmed.2005.03.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
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.
引用
收藏
页码:232 / 239
页数:8
相关论文
共 63 条
[1]
The c-Jun amino-terminal kinase pathway is preferentially activated by interleukin-1 and controls apoptosis in differentiating pancreatic β-cells [J].
Ammendrup, A ;
Maillard, A ;
Nielsen, K ;
Andersen, NA ;
Serup, P ;
Madsen, OD ;
Mandrup-Poulsen, T ;
Bonny, C .
DIABETES, 2000, 49 (09) :1468-1476
[2]
Protection against malonate-induced ischemic brain injury in rat by a cell-permeable peptidic c-Jun N-terminal kinase inhibitor, (L)-H1V-TAT48-57-PP-JBD20, observed by the apparent diffusion coefficient mapping magnetic resonance imaging method [J].
Asanuma, T ;
Inanami, O ;
Tabu, K ;
Waki, K ;
Kon, Y ;
Kuwabara, M .
NEUROSCIENCE LETTERS, 2004, 359 (1-2) :57-60
[3]
The specificities of protein kinase inhibitors: an update [J].
Bain, J ;
McLauchlan, H ;
Elliott, M ;
Cohen, P .
BIOCHEMICAL JOURNAL, 2003, 371 :199-204
[4]
Reverse two-hybrid screening identifies residues of JNK required for interaction with the kinase interaction motif of JNK-interacting protein-1 [J].
Barr, RK ;
Hopkins, RM ;
Watt, PM ;
Bogoyevitch, MA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (41) :43178-43189
[5]
The critical features and the mechanism of inhibition of a kinase interaction motif-based peptide inhibitor of JNK [J].
Barr, RK ;
Boehm, I ;
Attwood, PV ;
Watt, PM ;
Bogoyevitch, MA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (35) :36327-36338
[6]
Identification of the critical features of a small peptide inhibitor of JNK activity [J].
Barr, RK ;
Kendrick, TS ;
Bogoyevitch, MA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (13) :10987-10997
[7]
SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase [J].
Bennett, BL ;
Sasaki, DT ;
Murray, BW ;
O'Leary, EC ;
Sakata, ST ;
Xu, WM ;
Leisten, JC ;
Motiwala, A ;
Pierce, S ;
Satoh, Y ;
Bhagwat, SS ;
Manning, AM ;
Anderson, DW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (24) :13681-13686
[8]
Targeting the JNK MAPK cascade for inhibition: basic science and therapeutic potential [J].
Bogoyevitch, MA ;
Boehm, I ;
Oakley, A ;
Ketteman, AJ ;
Barr, RK .
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, 2004, 1697 (1-2) :89-101
[9]
Targeting MAPK signalling: Prometheus' fire or pandora's box? [J].
Boldt, S ;
Kolch, W .
CURRENT PHARMACEUTICAL DESIGN, 2004, 10 (16) :1885-1905
[10]
Cell-permeable peptide inhibitors of JNK novel blockers of β-cell death [J].
Bonny, C ;
Oberson, A ;
Negri, S ;
Sauser, C ;
Schorderet, DF .
DIABETES, 2001, 50 (01) :77-82