ArticlePloS one2019
Preclinical evaluation of EPHX2 inhibition as a novel treatment for inflammatory bowel disease.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 35 citations in OpenAlex.
- Experimental Characterization Combined with Computational Network Analysis of Metabolites Associated with Chrysanthemum morifolium-derived exosome-like Nanoparticles in Predicting Potential AKI-relevant Targets.Cell biochemistry and biophysics · 2026Article
- Design and Synthesis of Novel sEH Inhibitors for the Treatment of Inflammatory Bowel Disease.Journal of medicinal chemistry · 2025Article
- Identification of Potential Functional Modules and Diagnostic Genes for Crohn's Disease Based on Weighted Gene Co-expression Network Analysis and LASSO Algorithm.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2025Article
- Identification and Validation of Feature Genes Related to Mitochondrial Dysfunction and Oxidative Stress in Ulcerative Colitis.Journal of inflammation research · 2025Article
- Regulating arachidonic acid metabolism: a novel strategy to prevent colorectal inflammatory cancer transformation.Journal of Cancer · 2025Review
- Causality of genetically determined blood metabolites on inflammatory bowel disease: a two-sample Mendelian randomization study.Scientific reports · 2024Article
- Discovery of the sEH Inhibitor Epoxykynin as a Potent Kynurenine Pathway Modulator.Journal of medicinal chemistry · 2024Article
- Article
- Aflatoxin BEcotoxicology and environmental safety · 2023Article
- High Glycemia and Soluble Epoxide Hydrolase in Females: Differential Multiomics in Murine Brain Microvasculature.International journal of molecular sciences · 2022Article
- Age-dependent changes of hindgut microbiota succession and metabolic function of Mongolian cattle in the semi-arid rangelands.Frontiers in microbiology · 2022Article
- Article
- Tofacitinib inhibits inflammatory cytokines from ulcerative colitis and healthy mucosal explants and is associated with pSTAT1/3 reduction in T-cells.American journal of physiology. Gastrointestinal and liver physiology · 2021Article
- Integrative computational approach identifies drug targets in CD4NPJ systems biology and applications · 2021Article
- The Multifaceted Role of Epoxide Hydrolases in Human Health and Disease.International journal of molecular sciences · 2020Review
- ω-3 Polyunsaturated Fatty Acids on Colonic Inflammation and Colon Cancer: Roles of Lipid-Metabolizing Enzymes Involved.Nutrients · 2020Review
- Soluble Epoxide Hydrolase Inhibition in Liver Diseases: A Review of Current Research and Knowledge Gaps.Biology · 2020Review
- Silencing of soluble epoxide hydrolase 2 gene reduces HCytotechnology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epoxyeicosatrienoic acids (EETs) are signaling lipids produced by cytochrome P450 epoxygenation of arachidonic acid, which are metabolized by EPHX2 (epoxide hydrolase 2, alias soluble epoxide hydrolase or sEH). EETs have pleiotropic effects, including anti-inflammatory activity. Using a Connectivity Map (CMAP) approach, we identified an inverse-correlation between an exemplar EPHX2 inhibitor (EPHX2i) compound response and an inflammatory bowel disease patient-derived signature. To validate the gene-disease link, we tested a pre-clinical tool EPHX2i (GSK1910364) in a mouse disease model, where it showed improved outcomes comparable to or better than the positive control Cyclosporin A. Up-regulation of cytoprotective genes and down-regulation of proinflammatory cytokine production were observed in colon samples obtained from EPHX2i-treated mice. Follow-up immunohistochemistry analysis verified the presence of EPHX2 protein in infiltrated immune cells from Crohn's patient tissue biopsies. We further demonstrated that GSK2256294, a clinical EPHX2i, reduced the production of IL2, IL12p70, IL10 and TNFα in both ulcerative colitis and Crohn's disease patient-derived explant cultures. Interestingly, GSK2256294 reduced IL4 and IFNγ in ulcerative colitis, and IL1β in Crohn's disease specifically, suggesting potential differential effects of GSK2256294 in these two diseases. Taken together, these findings suggest a novel therapeutic use of EPHX2 inhibition for IBD.
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.