Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, National Clinical Research Center for Geriatrics, West China Hospital, and West China second Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China.
Expert Opin Ther Pat. 2024 Oct;34(10):907-927. doi: 10.1080/13543776.2024.2400167. Epub 2024 Sep 8.
c-Jun N-terminal kinase (JNK) regulates various biological processes through the phosphorylation cascade and is closely associated with numerous diseases, including inflammation, cardiovascular diseases, and neurological disorders. Therefore, JNKs have emerged as potential targets for disease treatment.
This review compiles the patents and literatures concerning JNK inhibitors through retrieving relevant information from the SciFinder, Google Patents databases, and PubMed from 2015 to the present. It summarizes the structure-activity relationship (SAR) and biological activity profiles of JNK inhibitors, offering valuable perspectives on their potential therapeutic applications.
The JNK kinase serves as a novel target for the treatment of neurodegenerative disorders, pulmonary fibrosis, and other illnesses. A variety of small-molecule inhibitors targeting JNKs have demonstrated promising therapeutic potential in preclinical studies, which act upon JNK kinases via distinct mechanisms, encompassing traditional ATP competitive inhibition, covalent inhibition, and bidentate inhibition. Among them, several JNK inhibitors from PregLem SA, Celegene SA, and Xigen SA have accomplished the early stage of clinical trials, and their results will guide the development and indications of future JNK inhibitors.
c-Jun N-末端激酶(JNK)通过磷酸化级联反应调节各种生物过程,与许多疾病密切相关,包括炎症、心血管疾病和神经紊乱。因此,JNK 已成为疾病治疗的潜在靶点。
本综述通过从 2015 年至今的 SciFinder、Google Patents 数据库和 PubMed 中检索相关信息,汇总了 JNK 抑制剂的专利和文献。本文总结了 JNK 抑制剂的结构-活性关系(SAR)和生物学活性概况,为其潜在的治疗应用提供了有价值的视角。
JNK 激酶是治疗神经退行性疾病、肺纤维化和其他疾病的新靶点。多种针对 JNK 的小分子抑制剂在临床前研究中显示出有希望的治疗潜力,它们通过不同的机制作用于 JNK 激酶,包括传统的 ATP 竞争抑制、共价抑制和双齿抑制。其中,PregLem SA、Celegene SA 和 Xigen SA 的几种 JNK 抑制剂已完成临床试验的早期阶段,其结果将指导未来 JNK 抑制剂的开发和适应症。