Identification and characterization of a novel chemotype for human TLR8 inhibitors.
Identification and characterization of a novel chemotype for human TLR8 inhibitors.
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人类 TLR8 抑制剂新型化学型的鉴定和表征
DOI：
10.1016/j.ejmech.2019.06.084
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发表时间：
2019
影响因子：
6.7
通讯作者：
Wolber
中科院分区：
文献类型：
--
作者：
Sribar;Grabowski;Murgueitio;Bermudez;Weindl;Wolber
The endosomal Toll-like receptor 8 (TLR8) recognizes single-stranded RNA and initiates early inflammatory responses. Despite the importance of endosomal TLRs for human host defense against microbial pathogens, extensive activation may contribute to autoimmune and inflammatory diseases. In contrast to the recent progress made in the development of modulators of plasma membrane-bound TLRs, little is known about endosomal TLR modulation and very few TLR8 inhibitors have been reported. In this study, we discovered and validated novel small-molecule TLR8 inhibitors. Fourteen potential TLR8 modulators were experimentally validated in HEK293T cells stably overexpressing human TLR8 and THP-1 macrophages. Five compounds inhibited TLR8-mediated signaling, representing a hit rate of 36%. The three most potent compounds neither cause cellular toxicity nor inhibition of TLR signaling induced by other receptor subtypes. Conclusively, we experimentally confirm novel and selective, pyrimidine-based TLR8 inhibitors with low cytotoxicity that are relevant candidates for lead optimization and further mechanistic studies.
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影响因子：
4.8
作者：
Bock, Andreas;Bermudez, Marcel;Mohr, Klaus
通讯作者：
Mohr, Klaus
DOI：
10.1016/j.bbagen.2017.07.011
发表时间：
2017-11-01
影响因子：
3
作者：
Murgueitio, M. S.;Ebner, S.;Santos-Sierra, S.
通讯作者：
Santos-Sierra, S.
DOI：
10.1042/bj20131492
发表时间：
2014-03
期刊：
The Biochemical journal
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.6
作者：
Mortier J;Prévost JRC;Sydow D;Teuchert S;Omieczynski C;Bermudez M;Frédérick R;Wolber G
通讯作者：
Wolber G
影响因子：
16.6
作者：
Cheng, Kui;Wang, Xiaohui;Zhang, Shuting;Yin, Hang
通讯作者：
Yin, Hang