Evidence map›Paper›PMID 34272380›Full record

ArticleNature communications2021

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 and 7 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.1field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 3 countries.

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, Beijing, China.ORCID 0000-0003-0277-6139
Adam Csakai *Department of Chemistry & Biochemistry and the BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, USA.
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, Beijing, China.
Christina SmithDepartment of Chemistry & Biochemistry and the BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, USA.
Hiromi TanjiGraduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Jian HuangSchool 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, Beijing, China.
Torey JonesDepartment of Chemistry & Biochemistry and the BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, USA.
Kentaro SakaniwaGraduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Lindsey BroadwellDepartment of Chemistry & Biochemistry and the BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, USA.
Chengrui ShiSchool 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, Beijing, China.
Subada SotiDepartment of Chemistry & Biochemistry and the BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, USA.
Umeharu OhtoGraduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.ORCID 0000-0002-4422-4044
Yaohui FangWuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Shu ShenWuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.ORCID 0000-0002-0013-5365
Fei DengWuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.ORCID 0000-0002-5385-083X
Toshiyuki ShimizuGraduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.ORCID 0000-0002-0547-8922
Hang YinSchool 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, Beijing, China. yin_hang@tsinghua.edu.cn.ORCID 0000-0002-9762-4818
University of Colorado Boulder · USCenter for Life Sciences · CNThe University of Tokyo · JPChinese Academy of Sciences · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Small-molecule modulators of TLR8 have drawn much interests as it plays pivotal roles in the innate immune response to single-stranded RNAs (ssRNAs) derived from viruses. However, their clinical uses are limited because they can invoke an uncontrolled, global inflammatory response. The efforts described herein culminate in the fortuitous discovery of a tetrasubstituted imidazole CU-CPD107 which inhibits R848-induced TLR8 signaling. In stark contrast, CU-CPD107 shows unexpected synergistic agonist activities in the presence of ssRNA, while CU-CPD107 alone is unable to influence TLR8 signaling. CU-CPD107's unique, dichotomous behavior sheds light on a way to approach TLR agonists. CU-CPD107 offers the opportunity to avoid the undesired, global inflammation side effects that have rendered imidazoquinolines clinically irrelevant, providing an insight for the development of antiviral drugs.

Indexed as

CalorimetryHEK293 CellsHumansImidazolesInflammationMolecular Docking SimulationQuinolinesRecombinant ProteinsRNASignal TransductionStructure-Activity RelationshipToll-Like Receptor 8X-Ray Diffraction1-(2-methylpropyl)-1H-imidazo(4,5-c)quinolin 4-amineImidazolesQuinolinesRecombinant ProteinsresiquimodRNATLR8 protein, humanToll-Like Receptor 8

Identifiers

PMID34272380
PMCPMC8285539
OpenAlexW3178465786

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.