期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 65, 期 5, 页码 3758-3775出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.1c01947
关键词
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资金
- National Natural Science Foundation of China [22177083, 81922064, 81803755, 81874290]
- Sichuan University Postdoctoral Interdisciplinary Innovation Fund
- National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University [Z20201004]
- West China Nursing Discipline Development Special Fund Project, Sichuan University [HXHL21011]
This article introduces the JNK signaling pathways and different chemical types of JNK inhibitors, focusing on their structure-activity relationships and biological activities. The challenges and strategies for the development of JNK inhibitors are also discussed. It provides valuable references for the development of novel selective JNK inhibitors.
c-Jun N-terminal kinases (JNKs), members of the mitogen-activated protein kinase (MAPK) family, are encoded by three genes: jnk1, jnk2, and jnk3. JNKs are involved in the pathogenesis and development of many diseases, such as neurodegenerative diseases, inflammation, and cancers. Therefore, JNKs have become important therapeutic targets. Many JNK inhibitors have been discovered, and some have been introduced into clinical trials. However, the study of isoform-selective JNK inhibitors is still a challenging task. To further develop novel JNK inhibitors with clinical value, a comprehensive understanding of JNKs and their corresponding inhibitors is required. In this Perspective, we introduced the JNK signaling pathways and reviewed different chemical types of JNK inhibitors, focusing on their structure-activity relationships and biological activities. The challenges and strategies for the development of JNK inhibitors are also discussed. It is hoped that this Perspective will provide valuable references for the development of novel selective JNK inhibitors.
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