Abstract
Targeting protein kinases has been active area in drug discovery. The c-Jun N-terminal kinases (JNKs) have also been target for development of novel therapy in various diseases, since the roles of JNK signaling in pathological conditions were revealed in studies using jnk-deficient mice. Small molecule inhibitors and peptide inhibitors are identified for therapeutic intervention of JNK signaling pathway. SP-600125, an anthrapyrazole small molecule inhibitor for JNK with high potency and selectivity has been widely used for dissecting JNK signaling pathway. CC-401 is the first JNK inhibitor that went into clinical trial for inflammation and leukemia. Inhibitor for mixed lineage kinase (MLK), CEP-1347 also negatively regulates JNK signaling, and tried for potential use in Parkinson’s disease. Cell-permeable peptide inhibitor D-JNKI-1 is being developed for the treatment of hearing loss. The current status of these JNK inhibitors and safety issue is discussed in the minireview.
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Abbreviations
- JNK:
-
c-Jun N-terminal kinase
- ATP:
-
adenosine 5′-triphosphate
- MLK:
-
mixed lineage kinase
- EGFR:
-
epidermal growth factor receptor
- VEGFR:
-
vascular endothelial cell growth factor receptor
- MAPK:
-
mitogen-activated protein kinase
- MAP2K/MKK:
-
MAPK kinase
- MAP3K:
-
MAPK kinase kinase
- MEK:
-
MAPK-ERK kinase
- ERK:
-
extracellular signal-regulated kinase
- Ki:
-
inhibitory constant
- IKK:
-
IκB kinase
- IC50:
-
concentration of compound to achieve 50% inhibition
- CDK:
-
cyclin-dependent kinase
- MPTP:
-
1-methyl-4-phenyl tetrahydro-pyridine
- JBD:
-
JNK-binding domain
- JIP:
-
JNK-interacting protein
- IL-1β:
-
interleukin-1β
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Han, SY. c-Jun N-Terminal Kinase Signaling Inhibitors Under Development. Toxicol Res. 24, 93–100 (2008). https://doi.org/10.5487/TR.2008.24.2.093
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DOI: https://doi.org/10.5487/TR.2008.24.2.093