Nature Communications (Jul 2021)
Tetrasubstituted imidazoles as incognito Toll-like receptor 8 a(nta)gonists
- Yi Yang,
- Adam Csakai,
- Shuangshuang Jiang,
- Christina Smith,
- Hiromi Tanji,
- Jian Huang,
- Torey Jones,
- Kentaro Sakaniwa,
- Lindsey Broadwell,
- Chengrui Shi,
- Subada Soti,
- Umeharu Ohto,
- Yaohui Fang,
- Shu Shen,
- Fei Deng,
- Toshiyuki Shimizu,
- Hang Yin
Affiliations
- Yi Yang
- School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University
- Adam Csakai
- Department of Chemistry & Biochemistry and the BioFrontiers Institute, University of Colorado Boulder
- Shuangshuang Jiang
- School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University
- Christina Smith
- Department of Chemistry & Biochemistry and the BioFrontiers Institute, University of Colorado Boulder
- Hiromi Tanji
- Graduate School of Pharmaceutical Sciences, The University of Tokyo
- Jian Huang
- School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University
- Torey Jones
- Department of Chemistry & Biochemistry and the BioFrontiers Institute, University of Colorado Boulder
- Kentaro Sakaniwa
- Graduate School of Pharmaceutical Sciences, The University of Tokyo
- Lindsey Broadwell
- Department of Chemistry & Biochemistry and the BioFrontiers Institute, University of Colorado Boulder
- Chengrui Shi
- School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University
- Subada Soti
- Department of Chemistry & Biochemistry and the BioFrontiers Institute, University of Colorado Boulder
- Umeharu Ohto
- Graduate School of Pharmaceutical Sciences, The University of Tokyo
- Yaohui Fang
- Wuhan Institute of Virology, Chinese Academy of Sciences
- Shu Shen
- Wuhan Institute of Virology, Chinese Academy of Sciences
- Fei Deng
- Wuhan Institute of Virology, Chinese Academy of Sciences
- Toshiyuki Shimizu
- Graduate School of Pharmaceutical Sciences, The University of Tokyo
- Hang Yin
- School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University
- DOI
- https://doi.org/10.1038/s41467-021-24536-4
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 9
Abstract
Toll-like receptor 8 (TLR8) plays essential roles in the innate immune response to viral single-stranded RNA (ssRNA), so small molecule modulators of TLR8 are of interest, however adverse effects limit their use. Here, the authors report a tetrasubstituted imidazole CU-CPD107 with dichotomous behaviour, which inhibits R848-induced TLR8 signaling, but shows synergistic activity in the presence of ssRNA, making it a potential antiviral agent.
