化学
痛风
脚手架
鉴定(生物学)
药物发现
组合化学
计算生物学
药理学
纳米技术
生物化学
植物
材料科学
生物
医学
生物医学工程
作者
Cheng Shi,Weiping Lyu,Jie Yu,Yanming Chen,Siyu Xiu,Qian Zhang,Liangren Zhang,Zhenming Liu
标识
DOI:10.1016/j.ejmech.2024.116881
摘要
Gout as a common inflammatory arthritis seriously affects the quality of life of a large number of people. Targeting NLRP3 inflammasome has been certified as a promising therapeutic strategy for gout. This study, a series of new imidazolidinone derivatives were validated as NLRP3 inhibitors by scaffold hopping from the reported NLRP3 inhibitor CSC-6. In contrast to the poor physicochemical properties of the template molecule, the representative compound 23 showed good plasma stability, water solubility, and no significant inhibitory toxicity to CYP450 enzymes. Surface plasmon resonance and immunoblotting experiments showed that compound 23 binds NLRP3 and inhibits NLRP3 activation. Finally, compound 23 showed good anti-inflammatory and analgesic effects in acute peritonitis and arthritis. Overall, the present study provides NLRP3 inhibitors with favorable pharmacological properties, which may not only serve as a tool molecule for studying NLRP3-related functions, but also may further facilitate the gout treatment.
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