Recent Advances in c-Jun N-terminal Kinase (JNK) Inhibitors

2020 
c-Jun N-terminal kinases (JNKs), members of the Mitogen-activated protein kinase (MAPK) signaling pathway, play a key role in the pathogenesis of many diseases including cancer, inflammation, Parkinson's disease, Alzheimer's disease, cardiovascular disease, obesity, and diabetes. Therefore, JNKs represent new and excellent target by therapeutic agents. Many JNK inhibitors based on different molecular scaffolds have been discovered in the past decade. However, only a few of them have advanced to clinical trials. The major obstacle for the development of JNK inhibitors as therapeutic agents is the JNK-isoform selectivity. In this review, we describe the recent development of JNK inhibitors including ATP competitive and ATP non-competitive (allosteric) inhibitors, bidentate-binding inhibitors and dual inhibitors, the challenges, and future direction of JNK inhibitors as potential therapeutic agents.
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