SMTP: Modulators of Plasminogen Function
This class of compounds is called SMTP because they were purified from the culture of the filamentous fungus Stachybotrys microspora (SM) and have a structure of triprenyl phenol (TP). SMTP compounds resemble the structure of vitamin E and have unique biological activity associated with enhancement of the fibrinolytic system. The culture may produce a variety of SMTP compounds depending on the precursor compounds added to the culture medium. TMS has already identified more than 50 compounds from the culture.
It is well appreciated that the fibrinolytic system is associated with a variety of pathophysiological activities including angiogenesis (blood vessel formation), cancer invasion and metastases, inflammation, ovulation and ovum implantation, and tissue repair and remodeling in addition to thrombolysis. In particular, the activation of plasminogen to plasmin, which is enhanced by a SMTP, regulates the local extracellular proteolysis and plays critical roles in the fibrinolytic system.
TMS has confirmed that the SMTP compounds developed in-house have shown activity in the following areas
- Anti-angiogenesis in cancer
- Thrombolytic activity
- Improvement in liver and kidney functions as well as metabolic function
- Anti-ageing activity in skin that is likely related to anti-oxidation activity and enhancement of tissue regeneration.
Accordingly, the newly discovered SMTP compounds are highly interesting potential products for medical and cosmeceutical use.
Mechanism of Action
SMTP molecules induce a conformation change of plasminogen that results in acceleration of plasminogen binding to fibrin and the resultant activation to plasmin. In addition, SMTP induces self-cleavage of plasmin to afford angiostatin-like fragments. This activity is believed to be the mechanism behind the anti-angiogenesis and anti-tumor effect of the SMTP molecules. In addition, the SMTP-induced increase in activated plasminogen may control local extracellular proteolysis that results in the induction of tissue remodeling, wound healing, and tissue regeneration.
It is important to note that SMTP molecules only act to relax the conformation of plasminogen. The actual activation of the plasminogen is executed by plasminogen activator, uPA or tPA. In a healthy person, endogenous plasmin levels are regulated by the body to ensure that sufficient quantities are produced to maintain healthy tissues. Research shows that lowered plasmin levels are associated with a variety of pathological conditions. TMS believes that SMTP may act to relax the tight conformation of plasminogen thereby increasing the rate of formation and quantity of plasmin in deficient or diseased tissues.
Pharmacological and Cosmeceutical Activity
Activities of SMTP molecules include the following:
- Thrombolysis (particularly for thrombembolism)
- Anti-angiogenesis activity on cancer
- Treatment of organ failure associated with a fibrous matrix protein accumulation
- Anti-aging in skin