Impact of SMTP Targeting Plasminogen and Soluble Epoxide Hydrolase on Thrombolysis, Inflammation, and Ischemic Stroke

Abstract

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.

Related Factors of Cerebral Hemorrhage after Cerebral Infarction and the Effect of Atorvastatin Combined with Intensive Nursing Care

“…The coexistence of cerebral ischemia and cerebral hem-orrhage lesions can cause the complication of the disease, and the anticoagulant, thrombolytic, and antiplatelet drugs cannot be used normally in the presence of cerebral hemorrhage, which cannot achieve the desired effect in the treatment of acute cerebral infarction. Therefore, active prevention and treatment should be given to cerebral hemorrhage transformation [12][13][14][15]. Statins are competitive inhibitors of 3-hydroxy-3-methylglutarate monoacylase A reductase, which can reduce the synthesis of cholesterol in the liver, increase the activity of low-density lipoprotein receptor on the surface of liver cells through feedback regulation, and accelerate the clearance of low-density lipoprotein.…”

A Novel Marine Pyran-Isoindolone Compound Enhances Fibrin Lysis Mediated by Single-Chain Urokinase-Type Plasminogen Activator

“…In the fibrinolytic system, the activation of zymogen is an allosteric process. A large number of studies have shown that small molecular compounds with fibrinolytic activity are allosteric effectors in the process of zymogen activation [ 40 , 41 ]. Selecting the inhibitors, antagonists, or activators of enzymes is an effective pharmacological means for the treatment of various diseases.…”

Progress in Isoindolone Alkaloid Derivatives from Marine Microorganism: Pharmacology, Preparation, and Mechanism

“…The hemostatic system, consisting of the coagulation and fibrinolytic systems, is a vital physiological function in inhibiting hemorrhage and accelerating wound healing [1,2]. Fibrinolysis is regulated by plasminogen and activated by physiologic plasminogen activators: tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA).…”

“…Moreover, clot clearance of compound 1 was enhanced, further, in combination with u-PA [23]. At present, more than 60 congeners of staplabin have been isolated, which not only performed fibrinolysis activity but also exhibited various effects, such as anti-inflammatory, neuroprotection, and anti-cancer properties [1]. Other modified derivatives and structurefunction relationships of compound 1 have also been studied.…”