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Impact of SMTP Targeting Plasminogen and Soluble Epoxide Hydrolase on Thrombolysis, Inflammation, and Ischemic Stroke
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Impact of SMTP Targeting Plasminogen and Soluble Epoxide Hydrolase on Thrombolysis, Inflammation, and Ischemic Stroke
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Journal Article
Impact of SMTP Targeting Plasminogen and Soluble Epoxide Hydrolase on Thrombolysis, Inflammation, and Ischemic Stroke
2021
Overview
Stachybotrys microspora triprenyl phenol (SMTP) is a large family of small molecules derived from the fungus S. microspora. SMTP acts as a zymogen modulator (specifically, plasminogen modulator) that alters plasminogen conformation to enhance its binding to fibrin and subsequent fibrinolysis. Certain SMTP congeners exert anti-inflammatory effects by targeting soluble epoxide hydrolase. SMTP congeners with both plasminogen modulation activity and anti-inflammatory activity ameliorate various aspects of ischemic stroke in rodents and primates. A remarkable feature of SMTP efficacy is the suppression of hemorrhagic transformation, which is exacerbated by conventional thrombolytic treatments. No drug with such properties has been developed yet, and SMTP would be the first to promote thrombolysis but suppress disease-associated bleeding. On the basis of these findings, one SMTP congener is under clinical study and development. This review summarizes the discovery, mechanism of action, pharmacological activities, and development of SMTP.
Publisher
MDPI AG,MDPI
Subject
/ Anti-Inflammatory Agents - pharmacology
/ Anti-Inflammatory Agents - therapeutic use
/ Benzopyrans - therapeutic use
/ Brain Ischemia - drug therapy
/ Disease
/ Drugs
/ Epoxide Hydrolases - drug effects
/ Epoxide Hydrolases - metabolism
/ Fibrinolytic Agents - pharmacology
/ Fibrinolytic Agents - therapeutic use
/ Humans
/ Ischemic Stroke - drug therapy
/ Pyrrolidinones - pharmacology
/ Pyrrolidinones - therapeutic use
/ Review
/ Stroke
