دورية
Discovery of a dual-acting inhibitor of interleukin-1β and STATs for the treatment of inflammatory bowel diseaseElectronic supplementary information (ESI) available: The cytotoxicity profile for 10v; the 1H NMR, 13C NMR, and HRMS of all target compounds; and the HPLC purity of 10vare available free of charge. See DOI: https://doi.org/10.1039/d3md00451a
| العنوان: | Discovery of a dual-acting inhibitor of interleukin-1β and STATs for the treatment of inflammatory bowel diseaseElectronic supplementary information (ESI) available: The cytotoxicity profile for 10v; the 1H NMR, 13C NMR, and HRMS of all target compounds; and the HPLC purity of 10vare available free of charge. See DOI: https://doi.org/10.1039/d3md00451a |
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| المؤلفون: | Cai, Haowei, Liu, Zhuorong, Sun, Ping, Zhou, Yinghua, Yan, Yuyun, Luo, Yiming, Zhang, Xiuxiu, Wu, Ruiwen, Liang, Xiangting, Wu, Dan, Hu, Wenhui, Yang, Zhongjin |
| المصدر: | MedChemComm; 2024, Vol. 15 Issue: 1 p193-206, 14p |
| مستخلص: | Currently, a significant proportion of inflammatory bowel disease (IBD) patients fail to respond to conventional drug therapy such as immunosuppressants and biologic agents. Interference with the JAK/STAT pathway and blocking of IL-1 signaling are two promising therapeutic strategies for these unresponsive IBD patients. This work describes the discovery of an inhibitor 10vthat not only blocks NLRP3 and AIM-2 inflammasome-mediated IL-1β signaling, but also reduces the expression of STAT1 and STAT5 in the JAK/STAT pathway. Importantly, 10vexhibits a significant anti-IL-1β effect and decreases the levels of STAT1 and STAT5 in a mouse model of colitis. As a result, a novel small molecule is identified with a dual inhibitory capacity towards both inflammasomes/IL-1β and STAT pathways, which supports further exploration of the therapeutic potential for IBD patients that do not respond to current drug therapy. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 20402503 20402511 |
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| DOI: | 10.1039/d3md00451a |