ArticleJCI insight2018
From proteomics to discovery of first-in-class ST2 inhibitors active in vivo.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 38 citations in OpenAlex.
- Development of 2‑Methyl-5-phenylpyrrolidine-Based ST2 Inhibitors for Neuroinflammatory Conditions.ACS medicinal chemistry letters · 2026Article
- Drug Metabolism and Pharmacokinetics of Oxazolo[4,5-Pharmaceutics · 2025Article
- Activity-attenuated serum albumin-fused interleukin-33 suppresses experimental autoimmune encephalomyelitis.Cell reports. Medicine · 2025Article
- Dual targeting of tumoral cells and immune microenvironment by blocking the IL-33/IL1RL1 pathway.Nature communications · 2025Article
- Natriuretic Peptides and Soluble ST2 Improve Echocardiographic and Invasive Long-Term Survival Prediction in Patients Evaluated for Diastolic Dysfunction.International journal of molecular sciences · 2025Article
- Studies of Structure-Activity Relationship of 2-(Pyrrolidin-1ylmethyl)-1ACS medicinal chemistry letters · 2024Article
- Inserting "OFF-to-ON" BODIPY Tags into Cytokines: A Fluorogenic Interleukin IL-33 for Real-Time Imaging of Immune Cells.ACS central science · 2024Article
- Prophylactic Mitigation of Acute Graft versus Host Disease by Novel 2-(Pyrrolidin-1-ylmethyl)pyrrole-Based Stimulation-2 (ST2) Inhibitors.ACS pharmacology & translational science · 2023Article
- A Deep View of the Biological Property of Interleukin-33 and Its Dysfunction in the Gut.International journal of molecular sciences · 2023Review
- Validated graft-specific biomarkers identify patients at risk for chronic graft-versus-host disease and death.The Journal of clinical investigation · 2023Article
- Human Effectors of Acute and Chronic GVHD Overexpress CD83 and Predict Mortality.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Biomarkers for early complications post hematopoietic cell transplantation: Insights and challenges.Frontiers in immunology · 2023Review
- Structure-Activity relationship of 1-(Furan-2ylmethyl)Pyrrolidine-Based Stimulation-2 (ST2) inhibitors for treating graft versus host disease.Bioorganic & medicinal chemistry · 2022Article
- Discovery of small molecular inhibitors for interleukin-33/ST2 protein-protein interaction: a virtual screening, molecular dynamics simulations and binding free energy calculations.Molecular diversity · 2022Article
- Computational Cosolvent Mapping Analysis Leads to Identify Salicylic Acid Analogs as Weak Inhibitors of ST2 and IL33 Binding.The journal of physical chemistry. B · 2022Article
- Post-haematopoietic cell transplantation outcomes: why ST2 became a 'golden nugget' biomarker.British journal of haematology · 2021Review
- Myeloid Cells in Glioblastoma Microenvironment.Cells · 2020Review
- ICOSLScience translational medicine · 2020Article
- Glioma-derived IL-33 orchestrates an inflammatory brain tumor microenvironment that accelerates glioma progression.Nature communications · 2020Article
- ST2 as checkpoint target for colorectal cancer immunotherapy.JCI insight · 2020Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Soluble cytokine receptors function as decoy receptors to attenuate cytokine-mediated signaling and modulate downstream cellular responses. Dysregulated overproduction of soluble receptors can be pathological, such as soluble ST2 (sST2), a prognostic biomarker in cardiovascular diseases, ulcerative colitis, and graft-versus-host disease (GVHD). Although intervention using an ST2 antibody improves survival in murine GVHD models, sST2 is a challenging target for drug development because it binds to IL-33 via an extensive interaction interface. Here, we report the discovery of small-molecule ST2 inhibitors through a combination of high-throughput screening and computational analysis. After in vitro and in vivo toxicity assessment, 3 compounds were selected for evaluation in 2 experimental GVHD models. We show that the most effective compound, iST2-1, reduces plasma sST2 levels, alleviates disease symptoms, improves survival, and maintains graft-versus-leukemia activity. Our data suggest that iST2-1 warrants further optimization to develop treatment for inflammatory diseases mediated by sST2.
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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.