ArticleProceedings of the National Academy of Sciences of the United States of America2013
Design of a superior cytokine antagonist for topical ophthalmic use.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 30 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.
Phase I/IIa, Non-Randomised, Open-Label Dose Escalation and Expansion Trial With Isunakinra Alone and in Combination With a PD-1/PD-L1 Inhibitor in Patients With Metastatic or Unresectable, Locally Advanced Malignant Solid Tumors
A Phase IIa, Non-Randomized, Open-Label Dose Expansion Trial of Isunakinra in Combination With Pembrolizumab in Patients With Metastatic or Unresectable, Locally Advanced Colorectal Cancer
Who cites it
30 citing papers in PubMed.
- Targeting the double-edged sword: cytokines in the pathogenesis and treatment of autoimmune diseases.Inflammopharmacology · 2025Review
- Targeting cytokine and chemokine signaling pathways for cancer therapy.Signal transduction and targeted therapy · 2024Review
- IL-1 Receptor Dynamics in Immune Cells: Orchestrating Immune Precision and Balance.Immune network · 2024Review
- Developing a platform for secretion of biomolecules in Mycoplasma feriruminatoris.Microbial cell factories · 2024Article
- A phase 1 study of prophylactic anakinra to mitigate ICANS in patients with large B-cell lymphoma.Blood advances · 2023Article
- Strategies to therapeutically modulate cytokine action.Nature reviews. Drug discovery · 2023Review
- Extending the use of biologics to mucous membranes by attachment of a binding domain.Communications biology · 2023Article
- Non-Oncogene Addiction ofCancers · 2023Article
- Network Pharmacology Research Indicates that Wu-Mei-Wan Treats Obesity by Inhibiting Th17 Cell Differentiation and Alleviating Metabolic Inflammation.Combinatorial chemistry & high throughput screening · 2023Article
- Optimization of IL-1RA structure to achieve a smaller protein with a higher affinity to its receptor.Scientific reports · 2022Article
- Conformational Dynamics of the Soluble and Membrane-Bound Forms of Interleukin-1 Receptor Type-1: Insights into Linker Flexibility and Domain Orientation.International journal of molecular sciences · 2022Article
- The Therapeutic Prospects of Targeting IL-1R1 for the Modulation of Neuroinflammation in Central Nervous System Disorders.International journal of molecular sciences · 2022Review
- Synthesis of DPIE [2-(1,2-Diphenyl-1Molecules (Basel, Switzerland) · 2022Article
- Experimental Pharmacotherapy for Dry Eye Disease: A Review.Journal of experimental pharmacology · 2021Review
- Role for IL-1 Family Cytokines in Fungal Infections.Frontiers in microbiology · 2021Review
- Molecular Level Insights Into the Structural and Dynamic Factors Driving Cytokine Function.Frontiers in molecular biosciences · 2021Review
- Engineered ACE2 receptor traps potently neutralize SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Engineered ACE2 receptor traps potently neutralize SARS-CoV-2.bioRxiv : the preprint server for biology · 2020Article
- Comparative Analyses of the Conformational Dynamics Between the Soluble and Membrane-Bound Cytokine Receptors.Scientific reports · 2020Article
- Functional deficiency in endogenous interleukin-1 receptor antagonist in patients with febrile infection-related epilepsy syndrome.Annals of neurology · 2019Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
IL-1 is a key inflammatory and immune mediator in many diseases, including dry-eye disease, and its inhibition is clinically efficacious in rheumatoid arthritis and cryopyrin-associated periodic syndromes. To treat ocular surface disease with a topical biotherapeutic, the uniqueness of the site necessitates consideration of the agent's size, target location, binding kinetics, and thermal stability. Here we chimerized two IL-1 receptor ligands, IL-1β and IL-1Ra, to create an optimized receptor antagonist, EBI-005, for topical ocular administration. EBI-005 binds its target, IL-1R1, 85-fold more tightly than IL-1Ra, and this increase translates to an ∼100-fold increase in potency in vivo. EBI-005 preserves the affinity bias of IL-1Ra for IL-1R1 over the decoy receptor (IL-1R2), and, surprisingly, is also more thermally stable than either parental molecule. This rationally designed antagonist represents a unique approach to therapeutic design that can potentially be exploited for other β-trefoil family proteins in the IL-1 and FGF families.
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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.