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

[ Vol. 28 , Issue. 3 ]

Author(s):

Gang Li, Wenqing Qi, Xiaoxun Li, Jinwu Zhao, Meihua Luo and Jianjun Chen*   Pages 607 - 627 ( 21 )

Abstract:


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).

Affiliation:

Department of Oncology, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan 528300, Department of Pathology, St. Jude Children’s Research Hospital, Memphis TN 38105, Chengdu Easton Biopharmaceuticals Co., Ltd., Chengdu 611731, School of Pharmacy, Guangdong Medical University, Songshan Lake Science and Technology Industry Park, Dongguan 523808, Department of Oncology, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan 528300, Department of Oncology, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan 528300



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