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KMID : 0379520080240020093
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한국독성학회지
2008 Volume.24 No. 2 p.93 ~ p.100
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c-Jun N-Terminal Kinase Signaling Inhibitors Under Development
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Han Sun-Young
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Abstract
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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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KEYWORD
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JNK, Inhibitors, SP-600125, CC-401, AS-602801, CEP-1347, D-JNKI-1
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