ArticleThe Journal of antibiotics2015
Structure-activity relationships of the plasminogen modulator SMTP with respect to the inhibition of soluble epoxide hydrolase.
Article in The Journal of antibiotics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 23 citations in OpenAlex.
- Anti-Inflammatory Thrombolytic JX10 (TMS-007) in Late Presentation of Acute Ischemic Stroke.Stroke · 2024Trial
- Recent advancement of novel marine fungi derived secondary metabolite fibrinolytic compound FGFC in biomedical applications: a review.Frontiers in cellular and infection microbiology · 2024Review
- Semisynthetic Approach toward Biologically Active Derivatives of Phenylspirodrimanes fromACS omega · 2022Article
- 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
- N-Substituted amino acid inhibitors of the phosphatase domain of the soluble epoxide hydrolase.Biochemical and biophysical research communications · 2019Article
- Efficacy of SMTP-7, a small-molecule anti-inflammatory thrombolytic, in embolic stroke in monkeys.Pharmacology research & perspectives · 2018Article
- Prospective for cytochrome P450 epoxygenase cardiovascular and renal therapeutics.Pharmacology & therapeutics · 2018Review
- Confirmation of the absolute configuration of Stachybotrin C using single-crystal X-ray diffraction analysis of its 4-bromobenzyl ether derivative.The Journal of antibiotics · 2018Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A family of fungal metabolites, SMTP, is a small-molecule plasminogen modulator that enhances plasminogen activation, leading to thrombolysis. We recently demonstrated that SMTP-7 effectively treats ischemic stroke due to its thrombolytic activity as well as anti-inflammatory action, which is attributable to soluble epoxide hydrolase (sEH) inhibition. In this paper, we studied detailed structure-activity relationships of plasminogen modulation and sEH inhibition using 25 SMTP congeners including six newly synthesized ones. The results clearly demonstrate that the structure of the N-linked side chain of SMTP congeners markedly affect their activities toward plasminogen modulation and inhibitions of the two activities of sEH (C-terminal epoxide hydrolase and N-terminal phosphatase). A slight change in the N-linked side chain results in affording selectivity of SMTP congeners. Many congeners, which lacked plasminogen modulation activity, differently inhibited the two sEH activities depending on the structures of the N-linked side chain. Some congeners were active in plasminogen modulation and inhibition of both activities of sEH. These results help comprehensive understanding of ideal design of a drug useful for ischemic diseases that are associated with inflammation, such as stroke.
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