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

Author(s): Gang Li, Wenqing Qi, Xiaoxun Li, Jinwu Zhao, Meihua Luo, Jianjun Chen*

Journal Name: Current Medicinal Chemistry

Volume 28 , Issue 3 , 2021

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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 JNKisoform selectivity. In this review, we describe the recent development of JNK inhibitors, including ATP competitive and ATP non-competitive (allosteric) inhibitors, bidentatebinding inhibitors and dual inhibitors, the challenges, and the future direction of JNK inhibitors as potential therapeutic agents.

Keywords: JNK, inhibitors, ATP binding site, JNK isoform-selective, allosteric, bidentate, Mitogen-activated Protein Kinase (MAPK).

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Article Details

Year: 2021
Published on: 01 February, 2021
Page: [607 - 627]
Pages: 21
DOI: 10.2174/0929867327666200210144114
Price: $65

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PDF: 152