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Cover Picture: Pyrimidine Triazole Thioether Derivatives as Toll‐Like Receptor 5 (TLR5)/Flagellin Complex Inhibitors (ChemMedChem 8/2016)
Author(s) -
Yan Lei,
Liang Jiaqi,
Yao Chengbo,
Wu Peiyao,
Zeng Xianfeng,
Cheng Kui,
Yin Hang
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201600184
Subject(s) - tlr5 , flagellin , chemistry , docking (animal) , small molecule , microbiology and biotechnology , toll like receptor , receptor , biochemistry , innate immune system , biology , medicine , nursing
The front cover picture shows the successful development of a series of novel small‐molecule inhibitors of TLR5–Flagellin binding. If cells were thought of as light bulbs, the innate immune protein TLR5 and pathogen‐associated molecule pattern (PAMP) protein Flagellin could associate and turn the proinflammatory signaling on. When the TLR5 “plugs into” the Flagellin “socket” and forms a heterotetramer, the circuit is completed, resulting in inflammatory responses in cells. Small‐molecule inhibitors of this interaction were designed, and in particular, compound TH1020 (4‐((4‐benzyl‐5‐(pyridin4yl)‐4 H ‐1,2,4‐triazol‐3‐yl)thio)pyrido[3′,2′:4,5]thieno[3,2‐ d ]pyrimidine) was identified as a potent and selective antagonist of TLR5 signaling with promising activity (IC 50 =0.85±0.12 μ m ). Computational docking analysis suggests that TH1020 competes with Flagellin binding to TLR5, thus “turning off” the cell “bulbs” and ultimately suppressing inflammation. More information can be found in the Communication by Hang Yin, et al. on page 822 in Issue 8, 2016 (DOI: 10.1002/cmdc.201500471).