ArticleThe Journal of pharmacology and experimental therapeutics2014
Detailed mechanistic analysis of gevokizumab, an allosteric anti-IL-1β antibody with differential receptor-modulating properties.
Article in The Journal of pharmacology and experimental therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled 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.
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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Interleukin-1 blockade treatment decreasing cardiovascular risk.Clinical cardiology · 2019Pooled it
- Emerging Role of the NLRP3 Inflammasome in the Onset of Oral Diseases and Its Potential as a Therapeutic Target.International journal of molecular sciences · 2026Review
- Review
- Article
- Soluble immune mediators orchestrate protectiveeLife · 2025Article
- Role of inflammasomes in cancer immunity: mechanisms and therapeutic potential.Journal of experimental & clinical cancer research : CR · 2025Review
- Discovery and Phase 1 study of a novel monoclonal antibody against human IL-1β for the treatment of IL-1β-mediated diseases.Clinical and experimental immunology · 2025Article
- Competitive Epitope Binning Using HT-SPR.Methods in molecular biology (Clifton, N.J.) · 2025Article
- A Meta-Analysis Methodology in Stan to Estimate Population Pharmacokinetic Parameters from Multiple Aggregate Concentration-Time Datasets: Application to Gevokizumab mPBPK Model.Pharmaceutics · 2024Article
- The role of inflammasomes in human diseases and their potential as therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Immunological Approaches in the Treatment of Diabetic Nephropathy.Current diabetes reviews · 2024Review
- Key Factor Regulating Inflammatory Microenvironment, Metastasis, and Resistance in Breast Cancer: Interleukin-1 Signaling.Mediators of inflammation · 2021Review
- Interleukin-6 signaling requires only few IL-6 molecules: Relation to physiological concentrations of extracellular IL-6.Immunity, inflammation and disease · 2020Article
- A potential peptide derived from cytokine receptors can bind proinflammatory cytokines as a therapeutic strategy for anti-inflammation.Scientific reports · 2019Article
- Probing Anti-inflammatory Properties Independent of NF-κB Through Conformational Constraint of Peptide-Based Interleukin-1 Receptor Biased Ligands.Frontiers in chemistry · 2019Article
- Multiscale Coupling of an Agent-Based Model of Tissue Fibrosis and a Logic-Based Model of Intracellular Signaling.Frontiers in physiology · 2019Article
- DPIE [2-(1,2-diphenyl-1H-indol-3-yl)ethanamine] Augments Pro-Inflammatory Cytokine Production in IL-1β-Stimulated Primary Human Oral Cells.International journal of molecular sciences · 2018Article
- A Review of the Landscape of Targeted Immunomodulatory Therapies for Non-Infectious Uveitis.Ophthalmology and therapy · 2018Review
- Effect of Gevokizumab on Interleukin-1β-Mediated Cytochrome P450 3A4 and Drug Transporter Repression in Cultured Human Hepatocytes.European journal of drug metabolism and pharmacokinetics · 2017Article
- Discovery of a junctional epitope antibody that stabilizes IL-6 and gp80 protein:protein interaction and modulates its downstream signaling.Scientific reports · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Interleukin-1β (IL-1β) is a proinflammatory cytokine that is implicated in many autoinflammatory disorders, but is also important in defense against pathogens. Thus, there is a need to safely and effectively modulate IL-1β activity to reduce pathology while maintaining function. Gevokizumab is a potent anti-IL-1β antibody being developed as a treatment for diseases in which IL-1β has been associated with pathogenesis. Previous data indicated that gevokizumab negatively modulates IL-1β signaling through an allosteric mechanism. Because IL-1β signaling is a complex, dynamic process involving multiple components, it is important to understand the kinetics of IL-1β signaling and the impact of gevokizumab on this process. In the present study, we measured the impact of gevokizumab on the IL-1β system using Schild analysis and surface plasmon resonance studies, both of which demonstrated that gevokizumab decreases the binding affinity of IL-1β for the IL-1 receptor type I (IL-1RI) signaling receptor, but not the IL-1 counter-regulatory decoy receptor (IL-1 receptor type II). Gevokizumab inhibits both the binding of IL-1β to IL-1RI and the subsequent recruitment of IL-1 accessory protein primarily by reducing the association rates of these interactions. Based on this information and recently published structural data, we propose that gevokizumab decreases the association rate for binding of IL-1β to its receptor by altering the electrostatic surface potential of IL-1β, thus reducing the contribution of electrostatic steering to the rapid association rate. These data indicate, therefore, that gevokizumab is a unique inhibitor of IL-1β signaling that may offer an alternative to current therapies for IL-1β-associated autoinflammatory diseases.
Indexed as
Identifiers
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.