ArticleJournal of immunology (Baltimore, Md. : 1950)2013
A novel small-molecule enantiomeric analogue of traditional (-)-morphinans has specific TLR9 antagonist properties and reduces sterile inflammation-induced organ damage.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
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.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- TLR9-mediated innate immune signaling contributes to acetaminophen-induced injury in the developing lung.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Damage-associated molecular patterns (DAMPs) in diseases: implications for therapy.Molecular biomedicine · 2025Review
- Small molecule modulators of immune pattern recognition receptors.RSC chemical biology · 2023Review
- Investigation of Microbial Translocation,Cancers · 2022Article
- The Role of Gut-Derived Microbial Antigens on Liver Fibrosis Initiation and Progression.Cells · 2019Review
- Small molecules as theranostic agents in cancer immunology.Theranostics · 2019Review
- Effects of Toll‑like receptor 9 and CpG oligodeoxynucleotides 1826 on sodium taurocholate‑induced acute pancreatitis rats.Molecular medicine reports · 2018Article
- Role of Damage Associated Molecular Pattern Molecules (DAMPs) in Aneurysmal Subarachnoid Hemorrhage (aSAH).International journal of molecular sciences · 2018Review
- TLR9 activation via microglial glucocorticoid receptors contributes to degeneration of midbrain dopamine neurons.Nature communications · 2018Article
- A leukocyte activation test identifies food items which induce release of DNA by innate immune peripheral blood leucocytes.Nutrition & metabolism · 2018Article
- A Prominent Role of Interleukin-18 in Acetaminophen-Induced Liver Injury Advocates Its Blockage for Therapy of Hepatic Necroinflammation.Frontiers in immunology · 2018Article
- Drugging Membrane Protein Interactions.Annual review of biomedical engineering · 2016Review
- STAT3, a Key Parameter of Cytokine-Driven Tissue Protection during Sterile Inflammation - the Case of Experimental Acetaminophen (Paracetamol)-Induced Liver Damage.Frontiers in immunology · 2016Review
- Promising Therapy Candidates for Liver Fibrosis.Frontiers in physiology · 2016Review
- Toll-Like Receptor 9-Mediated Inflammation Triggers Alveolar Bone Loss in Experimental Murine Periodontitis.Infection and immunity · 2015Article
- Toll-like receptor signaling in colorectal cancer: carcinogenesis to cancer therapy.World journal of gastroenterology · 2014Review
- Immune mechanisms in acetaminophen-induced acute liver failure.Hepatobiliary surgery and nutrition · 2014Review
- Dihydropyrrolo[2,3-d]pyrimidines: Selective Toll-Like Receptor 9 Antagonists from Scaffold Morphing Efforts.ACS medicinal chemistry letters · 2014Article
- The Gordian Knot of dysbiosis, obesity and NAFLD.Nature reviews. Gastroenterology & hepatology · 2013Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
TLR9 is a key determinant of the innate immune responses in both infectious and sterile injury. Specific antagonism of TLR9 is of great clinical interest to reduce tissue damage in a wide range of pathologies, and has been approached by modification of nucleic acids, the recognized ligand for TLR9. Such oligonucleotide-derived pharmacotherapeutics have limitations in specificity for nucleic acid receptors, significant potential for immunologic recognition with generation of innate and adaptive immune responses, and limited bioavailability. We have identified enantiomeric analogues of traditional (-)-morphinans as having TLR9 antagonist properties on reporter cell lines. One of these analogues (COV08-0064) is demonstrated to be a novel small-molecule antagonist of TLR9 with greater specificity for TLR9 than oligo-based antagonists. COV08-0064 has wide bioavailability, including the s.c. and oral routes. It specifically inhibits the action of TLR9 antagonists on reporter cells lines and the production of cytokines by TLR9 agonists from primary cells. It also has efficacy in limiting TLR9-mediated sterile inflammation in in vivo models of acute liver injury and acute pancreatitis. The identification of a morphinan-based novel small-molecule structure with TLR9 antagonism is a significant step in expanding therapeutic strategies in the field of sterile inflammatory injury.
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What OpenQuestion holds
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.