2. Academic Validation
  3. Discovery, synthesis, and biological mechanism evaluation of novel quinoline derivatives as potent NLRP3 inhibitors

Discovery, synthesis, and biological mechanism evaluation of novel quinoline derivatives as potent NLRP3 inhibitors

  • Eur J Med Chem. 2025 May 5:289:117466. doi: 10.1016/j.ejmech.2025.117466.
Ruiwen Wu 1,  Yuyun Yan 1,  Zhuorong Liu 1,  Xiuxiu Zhang 1,  Yiming Luo 1,  Xiangting Liang 1,  Jianhui Lin 1,  Xulin Zeng 1,  Dan Wu 1,  Ping Sun 2,  Wenhui Hu 3,  Zhongjin Yang 4
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • 2 School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China. Electronic address: sun_ping@gzhmu.edu.cn.
  • 3 School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China. Electronic address: huwenhui@gzhmu.edu.cn.
  • 4 School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin, 300384, China. Electronic address: yangzhj23@email.tjut.edu.cn.
PMID: 40073532 DOI: 10.1016/j.ejmech.2025.117466
Abstract

Targeting NLRP3 is a highly promising strategy for treating uncontrolled inflammation, which can cause a wide range of diseases or promote disease progression. More NLRP3-targeting inhibitors with different scaffolds are needed to increase the chances of developing safe and effective NLRP3 inhibitors and treating inflammation in different tissues. Here, we discovered the novel quinoline analogues that exhibit potent inhibitory activity against the NLRP3/IL-1β pathway in J774A.1, BMDMs, and human peripheral blood cells. Mechanistic studies confirmed W16 may directly target NLRP3 and block the NLRP3 inflammasome assembly and activation. In vitro studies demonstrated that W16 has potent anti-inflammatory effects on DSS-induced ulcerative colitis model. Our findings demonstrated that W16 is a potential lead compound targeting NLRP3 and deserves further investigation for the treatment of NLRP3-related inflammatory diseases.

Keywords

Colitis; Inhibitor; NLRP3; Quinoline.

Figures
Products