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

Int J Mol Sci. 2021 Jan 19;22(2):954. doi: 10.3390/ijms22020954.

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.

Keywords: SMTP; Stachybotrys microspora; antioxidative; cerebral infarction; fibrinolysis; inflammation; plasminogen; soluble epoxide hydrolase; stroke; thrombolytic; triprenyl phenol.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Benzopyrans / pharmacology*
  • Benzopyrans / therapeutic use
  • Brain Ischemia / blood
  • Brain Ischemia / drug therapy
  • Brain Ischemia / pathology
  • Epoxide Hydrolases / drug effects
  • Epoxide Hydrolases / metabolism
  • Fibrinolysis / drug effects
  • Fibrinolytic Agents / pharmacology
  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Inflammation / blood
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Ischemic Stroke / blood
  • Ischemic Stroke / drug therapy*
  • Ischemic Stroke / pathology
  • Plasminogen / drug effects
  • Plasminogen / metabolism
  • Pyrrolidinones / pharmacology*
  • Pyrrolidinones / therapeutic use
  • Stachybotrys / chemistry
  • Stachybotrys / metabolism
  • Thrombolytic Therapy / methods*

Substances

  • Anti-Inflammatory Agents
  • Benzopyrans
  • Fibrinolytic Agents
  • Pyrrolidinones
  • SMTP 1
  • SMTP-0 compound
  • Plasminogen
  • Epoxide Hydrolases

Supplementary concepts

  • Stachybotrys microspora