ArticlePloS one2016
Molecular Determinants of GS-9620-Dependent TLR7 Activation.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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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.
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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.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Article
- A Pooled Analysis of Eight Clinical Studies Suggests a Link Between Influenza-Like Symptoms and Pharmacodynamics of the Toll-Like Receptor-7 Agonist Vesatolimod.Infectious diseases and therapy · 2024Article
- COVID-19 induced liver injury from a new perspective: Mitochondria.Mitochondrion · 2023Review
- Enhanced antitumoral activity of TLR7 agonists via activation of human endogenous retroviruses by HDAC inhibitors.Communications biology · 2021Article
- Agonist and antagonist ligands of toll-like receptors 7 and 8: Ingenious tools for therapeutic purposes.European journal of medicinal chemistry · 2020Review
- Significance and Role of Pattern Recognition Receptors in Malignancy.Archivum immunologiae et therapiae experimentalis · 2019Review
- Targeting Cellular and Tissue HIV Reservoirs With Toll-Like Receptor Agonists.Frontiers in immunology · 2019Review
- Ideal Cure for Hepatitis B Infection: The Target is in Sight.Journal of clinical and experimental hepatology · 2018Review
- Towards HBV curative therapies.Liver international : official journal of the International Association for the Study of the Liver · 2018Review
- Toward Elimination of Hepatitis B Virus Using Novel Drugs, Approaches, and Combined Modalities.Clinics in liver disease · 2016Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GS-9620 is an orally administered agonist of Toll-like receptor (TLR)7 currently being evaluated in clinical studies for the treatment of chronic HBV and HIV patients. GS-9620 has shown antiviral efficacy in preclinical models of chronic hepadnavirus infection in woodchuck as well as chimpanzee. However, the molecular determinants of GS-9620-dependent activation of TLR7 are not well defined. The studies presented here elucidate GS-9620 subcellular distribution and characterize its molecular interactions with human TLR7 using structure-guided mutational analysis. Based on our results we present a molecular model of TLR7 bound to GS-9620. We also determine that several coding SNPs had no effect on GS-9620-dependent TLR7 activation. In addition, our studies provide evidence that TLR7 exists in a ligand-independent oligomeric state and that, TLR7 activation by GS-9620 is likely associated with compound-induced conformational changes. Finally, we demonstrate that activation of NF-κB and Akt pathways in primary plasmacytoid dendritic cells occur as immediate downstream cellular responses to GS-9620 stimulation. The data presented here further our understanding of the molecular parameters governing TLR7 activation by GS-9620, and more generally by nucleos/tide-related ligands.
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Registered trials
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.