ArticlePLoS biology2009
Identification of human S100A9 as a novel target for treatment of autoimmune disease via binding to quinoline-3-carboxamides.
Article in PLoS biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 1 of them a synthesis that pooled it.
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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
189 citing papers in PubMed, 1 synthesis or guideline pooled it, 357 citations in OpenAlex.
- Efficacy of tasquinimod in men with metastatic castration-resistant prostate cancer: A meta-analysis of randomized controlled trials.Medicine · 2018Pooled it
- Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3-Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.Arthritis & rheumatology (Hoboken, N.J.) · 2017Trial
- Assessment of the bone scan index in a randomized placebo-controlled trial of tasquinimod in men with metastatic castration-resistant prostate cancer (mCRPC).Urologic oncology · 2014Trial
- Long-term survival and biomarker correlates of tasquinimod efficacy in a multicenter randomized study of men with minimally symptomatic metastatic castration-resistant prostate cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Trial
- CKD disrupts cardiac energy metabolism and aggravates cardiac inflammation, oxidative stress, and dysfunction post-infarction.Cardiovascular research · 2026Article
- Review
- Neutrophil-derived S100A8/A9 impairs megakaryocyte maturation in immune thrombocytopenia.Nature communications · 2026Article
- RAGE Signalling in Acute Inflammatory Disorders: Therapeutic Potential of Natural Products.Biomolecules · 2026Review
- Plasma S100 Calcium-Binding Protein A8/A9 and Cognitive Impairment After Acute Ischemic Stroke.Journal of the American Heart Association · 2026Article
- Targeted inhibition of M2 macrophages polarization via a PDC attenuates chronic pancreatitis through the PPARα pathway.iScience · 2026Article
- Peptides in the Diagnosis and Treatment of Pancreatic Cancer and Other Pancreatic Diseases from Basic Research to Clinical Translation.Drug design, development and therapy · 2026Review
- S100A8/A9 inhibition reduces splenic myelopoiesis and improves outcomes after stroke.Frontiers in immunology · 2026Article
- Targeting S100A9-mediated inflammation: a novel therapeutic approach for CLL.Blood advances · 2025Review
- Infant Viability in Severe Preeclampsia: Management Strategies and the Potential Role of Calprotectin-A Narrative Review.Children (Basel, Switzerland) · 2025Review
- Exploring the Relevance of S100A8 and S100A9 Proteins in Preeclampsia: A Narrative Review.International journal of molecular sciences · 2025Review
- Innate immune mechanisms hijacked by leukemia-initiating stem cells for selective advantage and immune evasion in Ptpn11-associated JMML.Cell reports · 2025Article
- Neutrophil-Endothelium Interaction Mediated by S100A9 Promotes Pulmonary Vascular Remodeling During Pulmonary Hypertension.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Virtual Probing on the Influence of CaCell biochemistry and biophysics · 2025Article
- Development of novel neutralizing single-chain fragment variable antibodies against S100A8.Scientific reports · 2025Article
- S100A8/A9 innate immune signaling as a distinct mechanism driving progression of smoking-related breast cancers.Oncogene · 2025Article
129 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite more than 25 years of research, the molecular targets of quinoline-3-carboxamides have been elusive although these compounds are currently in Phase II and III development for treatment of autoimmune/inflammatory diseases in humans. Using photoaffinity cross-linking of a radioactively labelled quinoline-3-carboxamide compound, we could determine a direct association between human S100A9 and quinoline-3-carboxamides. This interaction was strictly dependent on both Zn++ and Ca++. We also show that S100A9 in the presence of Zn++ and Ca++ is an efficient ligand of receptor for advanced glycation end products (RAGE) and also an endogenous Toll ligand in that it shows a highly specific interaction with TLR4/MD2. Both these interactions are inhibited by quinoline-3-carboxamides. A clear structure-activity relationship (SAR) emerged with regard to the binding of quinoline-3-carboxamides to S100A9, as well as these compounds potency to inhibit interactions with RAGE or TLR4/MD2. The same SAR was observed when the compound's ability to inhibit acute experimental autoimmune encephalomyelitis in mice in vivo was analysed. Quinoline-3-carboxamides would also inhibit TNFalpha release in a S100A9-dependent model in vivo, as would antibodies raised against the quinoline-3-carboxamide-binding domain of S100A9. Thus, S100A9 appears to be a focal molecule in the control of autoimmune disease via its interactions with proinflammatory mediators. The specific binding of quinoline-3-carboxamides to S100A9 explains the immunomodulatory activity of this class of compounds and defines S100A9 as a novel target for treatment of human autoimmune diseases.
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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.