2. Academic Validation
  3. Discovery of novel 8-hydroxyquinoline derivatives as NLRP3 inflammasome inhibitors with therapeutic potential for inflammatory bowel disease

Discovery of novel 8-hydroxyquinoline derivatives as NLRP3 inflammasome inhibitors with therapeutic potential for inflammatory bowel disease

  • Eur J Med Chem. 2025 Nov 15:298:118023. doi: 10.1016/j.ejmech.2025.118023.
Xiuxiu Zhang 1,  Ruiwen Wu 1,  Yuyun Yan 1,  Yiming Luo 1,  Zhipeng Wan 2,  Zhuorong Liu 1,  Xiangting Liang 1,  Jie Yang 1,  Dan Wu 1,  Ping Sun 3,  Wenhui Hu 4,  Zhongjin Yang 5
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • 2 Department of Pharmacy, General Hospital of Southern Theatre Command, Guangzhou, 510010, Guangdong, China.
  • 3 School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China. Electronic address: sun_ping@gzhmu.edu.cn.
  • 4 School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China. Electronic address: huwenhui@gzhmu.edu.cn.
  • 5 School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin, 300384, China. Electronic address: yangzhj23@email.tjut.edu.cn.
PMID: 40774066 DOI: 10.1016/j.ejmech.2025.118023
Abstract

The activation of the NLRP3 inflammasome occurs through two distinct phases-priming and activation-and plays a significant role in various diseases including inflammatory conditions, Cancer, and autoimmune disorders. Recent studies have highlighted its critical involvement in the development and progression of inflammatory bowel disease (IBD). In this study, we identified a novel 8-hydroxyquinoline derivative, compound 10, as a potent inhibitor of NLRP3 inflammasome activation. Mechanistic studies demonstrated that 10 disrupts key protein-protein interactions, including NEK7-NLRP3, NLRP3-NLRP3, NLRP3-ASC, and ASC-ASC, thereby preventing NLRP3 inflammasome activation. Notably, 10 exhibited significant anti-inflammatory efficacy in a DSS-induced ulcerative colitis model, highlighting its in vivo therapeutic potential.

Keywords

Hydroxyquinoline; IL-1β; Inflammasome; Inflammatory bowel disease.

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