ArticleThe Journal of biological chemistry2014
Soluble epoxide hydrolase as an anti-inflammatory target of the thrombolytic stroke drug SMTP-7.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
- Anti-Inflammatory Thrombolytic JX10 (TMS-007) in Late Presentation of Acute Ischemic Stroke.Stroke · 2024Trial
- A Double-Blind, Randomized, Placebo-Controlled Trial of Soluble Epoxide Hydrolase Inhibition in Patients with Aneurysmal Subarachnoid Hemorrhage.Neurocritical care · 2022Trial
- SMTP-44D Attenuates Renal Inflammatory/Oxidative Dysfunction in a Mouse Model of Ischemia-Reperfusion-Induced Acute Kidney Injury.International journal of molecular sciences · 2026Article
- Intradomain Allosteric Regulation of Soluble Epoxide Hydrolase by Its Substrates.International journal of molecular sciences · 2024Article
- Recent advancement of novel marine fungi derived secondary metabolite fibrinolytic compound FGFC in biomedical applications: a review.Frontiers in cellular and infection microbiology · 2024Review
- SMTP-44D Inhibits Atherosclerotic Plaque Formation in Apolipoprotein-E Null Mice Partly by Suppressing the AGEs-RAGE Axis.International journal of molecular sciences · 2023Article
- Amine-Regulated pri-SMTP Oxidation in SMTP Biosynthesis inJournal of fungi (Basel, Switzerland) · 2022Article
- Progress in Isoindolone Alkaloid Derivatives from Marine Microorganism: Pharmacology, Preparation, and Mechanism.Marine drugs · 2022Review
- SMTP-44D Exerts Antioxidant and Anti-Inflammatory Effects through Its Soluble Epoxide Hydrolase Inhibitory Action in Immortalized Mouse Schwann Cells upon High Glucose Treatment.International journal of molecular sciences · 2022Article
- Impact of SMTP Targeting Plasminogen and Soluble Epoxide Hydrolase on Thrombolysis, Inflammation, and Ischemic Stroke.International journal of molecular sciences · 2021Review
- SMTP-44D improves diabetic neuropathy symptoms in mice through its antioxidant and anti-inflammatory activities.Pharmacology research & perspectives · 2020Article
- Discovery of the First in Vivo Active Inhibitors of the Soluble Epoxide Hydrolase Phosphatase Domain.Journal of medicinal chemistry · 2019Article
- N-Substituted amino acid inhibitors of the phosphatase domain of the soluble epoxide hydrolase.Biochemical and biophysical research communications · 2019Article
- Poster Viewing Sessions PB01-B01 to PB03-V09.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Humble beginnings with big goals: Small molecule soluble epoxide hydrolase inhibitors for treating CNS disorders.Progress in neurobiology · 2019Review
- Efficacy of SMTP-7, a small-molecule anti-inflammatory thrombolytic, in embolic stroke in monkeys.Pharmacology research & perspectives · 2018Article
- Proinflammatory enzyme soluble epoxide hydrolase bridges obesity to colonic inflammation and potential carcinogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Soluble Epoxide Hydrolase Inhibition Attenuates MPTP-Induced Neurotoxicity in the Nigrostriatal Dopaminergic System: Involvement of α-Synuclein Aggregation and ER Stress.Molecular neurobiology · 2018Article
- Advances in the Understanding of Protein-Protein Interactions in Drug Metabolizing Enzymes through the Use of Biophysical Techniques.Frontiers in pharmacology · 2017Review
- Structure-activity relationships of the plasminogen modulator SMTP with respect to the inhibition of soluble epoxide hydrolase.The Journal of antibiotics · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although ischemic stroke is a major cause of death and disability worldwide, only a small fraction of patients benefit from the current thrombolytic therapy due to a risk of cerebral hemorrhage caused by inflammation. Thus, the development of a new strategy to combat inflammation during thrombolysis is an urgent demand. The small molecule thrombolytic SMTP-7 effectively treats ischemic stroke in several animal models with reducing cerebral hemorrhage. Here we revealed that SMTP-7 targeted soluble epoxide hydrolase (sEH) to suppress inflammation. SMTP-7 inhibited both of the two sEH enzyme activities: epoxide hydrolase (which inactivates anti-inflammatory epoxy-fatty acids) and lipid phosphate phosphatase. SMTP-7 suppressed epoxy-fatty acid hydrolysis in HepG2 cells in culture, implicating the sEH inhibition in the anti-inflammatory mechanism. The sEH inhibition by SMTP-7 was independent of its thrombolytic activity. The simultaneous targeting of thrombolysis and sEH by a single molecule is a promising strategy to revolutionize the current stroke therapy.
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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.