1. Synthesis and pharmacological validation of fluorescent diarylsulfonylurea analogues as NLRP3 inhibitors and imaging probes
- Author
-
Jiannan Zhao, Yongling Li, Jing Ma, Jingting Liu, Ruoxuan Xiao, Linlin Wang, Peng Li, Yinyan He, Feng Qian, Ao Zhang, Zhen-Liang Sun, and Chunyong Ding
- Subjects
Pharmacology ,Inflammation ,Lipopolysaccharides ,Inflammasomes ,Organic Chemistry ,Drug Discovery ,Caspase 1 ,Interleukin-1beta ,NLR Family, Pyrin Domain-Containing 3 Protein ,Humans ,General Medicine - Abstract
The NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) is a key cytosolic pattern recognition receptor that senses diverse pathogen- and host-originated threat signals. Aberrant activation of NLRP3 inflammasomes is closely associated with the pathogenesis of various complex inflammatory diseases. Nevertheless, the detailed regulation mechanism of NLRP3 inflammasome and its pathogenic roles in the inflammation progression remain to be fully elucidated. Fluorescent imaging with small molecule probe can provide valuable visualization information on the expression, occupancy and bio-distribution of target protein. Herein, we reported a series of diarylsulfonylurea NLRP3 fluorescent inhibitors bearing an amino benzodiazole fluorophore. Compared to the previously reported NLRP3 fluorescent probes, these inhibitors are more structurally concise and membrane permeable due to no additionally appended fluorophore via a linker. Among this series, compound 13a exhibited the most potent cellular NLRP3 inhibitory effect with an IC
- Published
- 2022