ArticlePloS one2009
Toward the discovery of vaccine adjuvants: coupling in silico screening and in vitro analysis of antagonist binding to human and mouse CCR4 receptors.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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.
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.
Who cites it
20 citing papers in PubMed, 58 citations in OpenAlex.
- Safety, tolerability, pharmacokinetics and pharmacodynamics of GSK2239633, a CC-chemokine receptor 4 antagonist, in healthy male subjects: results from an open-label and from a randomised study.BMC pharmacology & toxicology · 2013Trial
- A Narrative Review of the State of the Art of CCR4-Based Therapies in Cutaneous T-Cell Lymphomas: Focus on Mogamulizumab and Future Treatments.Antibodies (Basel, Switzerland) · 2024Review
- Next-Generation Adjuvants: Applying Engineering Methods to Create and Evaluate Novel Immunological Responses.Pharmaceutics · 2023Article
- Small Molecule CCR4 Antagonists Protect Mice fromBiomolecules · 2021Article
- Tumor resident regulatory T cells.Seminars in immunology · 2021Review
- Maximal Unbiased Benchmarking Data Sets for Human Chemokine Receptors and Comparative Analysis.Journal of chemical information and modeling · 2018Article
- Chimeric antigen receptor modified T cells that target chemokine receptor CCR4 as a therapeutic modality for T-cell malignancies.American journal of hematology · 2017Article
- Structural Analysis of Chemokine Receptor-Ligand Interactions.Journal of medicinal chemistry · 2017Review
- Post-HTS case report and structural alert: Promiscuous 4-aroyl-1,5-disubstituted-3-hydroxy-2H-pyrrol-2-one actives verified by ALARM NMR.Bioorganic & medicinal chemistry letters · 2015Article
- Diphtheria-toxin based anti-human CCR4 immunotoxin for targeting human CCR4(+) cells in vivo.Molecular oncology · 2015Article
- Effect of Different Adjuvants on Protection and Side-Effects Induced by Helicobacter suis Whole-Cell Lysate Vaccination.PloS one · 2015Article
- Immunosuppressive Mechanisms of Malignant Gliomas: Parallels at Non-CNS Sites.Frontiers in oncology · 2015Review
- Regulatory T cells as adjuvant target for enhancing the viral disease vaccine efficacy.Virusdisease · 2014Review
- Targeting Tregs in Malignant Brain Cancer: Overcoming IDO.Frontiers in immunology · 2013Article
- Current progress in Structure-Based Rational Drug Design marks a new mindset in drug discovery.Computational and structural biotechnology journal · 2013Review
- Comprehensive analysis of current approaches to inhibit regulatory T cells in cancer.Oncoimmunology · 2012Article
- Pharmacological modulation of chemokine receptor function.British journal of pharmacology · 2012Review
- Shifting the equilibrium in cancer immunoediting: from tumor tolerance to eradication.Immunological reviews · 2011Review
- Understanding infectious agents from an in silico perspective.Drug discovery today · 2011Review
- Src homology 3-interacting domain of Rv1917c of Mycobacterium tuberculosis induces selective maturation of human dendritic cells by regulating PI3K-MAPK-NF-kappaB signaling and drives Th2 immune responses.The Journal of biological chemistry · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundAdjuvants enhance or modify an immune response that is made to an antigen. An antagonist of the chemokine CCR4 receptor can display adjuvant-like properties by diminishing the ability of CD4+CD25+ regulatory T cells (Tregs) to down-regulate immune responses. METHODOLOGY: Here, we have used protein modelling to create a plausible chemokine receptor model with the aim of using virtual screening to identify potential small molecule chemokine antagonists. A combination of homology modelling and molecular docking was used to create a model of the CCR4 receptor in order to investigate potential lead compounds that display antagonistic properties. Three-dimensional structure-based virtual screening of the CCR4 receptor identified 116 small molecules that were calculated to have a high affinity for the receptor; these were tested experimentally for CCR4 antagonism. Fifteen of these small molecules were shown to inhibit specifically CCR4-mediated cell migration, including that of CCR4(+) Tregs. SIGNIFICANCE: Our CCR4 antagonists act as adjuvants augmenting human T cell proliferation in an in vitro immune response model and compound SP50 increases T cell and antibody responses in vivo when combined with vaccine antigens of Mycobacterium tuberculosis and Plasmodium yoelii in mice.
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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.