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PAI-1 Inhibition in experimental venous thrombosis

Maxim E Shaydakov1,2, Cory D Emal3, Joshua P Rainey4

  • 1Vascular and Endovascular Surgery, WellSpan Health, York, PA, USA.

Phlebology
|January 22, 2026
PubMed

Insights

A new PAI-1 inhibitor, MDI-2268, shows significant antithrombotic effects in a mouse model of venous thrombosis. This novel pro-fibrinolytic agent effectively reduces thrombus weight without increasing bleeding time.

Area of Science:

  • Pharmacology
  • Thrombosis Research
  • Drug Development

Background:

  • Plasminogen activator inhibitor-1 (PAI-1) plays a key role in thrombosis.
  • A novel PAI-1 inhibitor, MDI-2268, has been developed.
  • Evaluating the efficacy and safety of MDI-2268 is crucial for potential therapeutic applications.

Purpose of the Study:

  • To assess the antithrombotic effects of MDI-2268 in an in vivo model of acute venous thrombosis (VT).
  • To evaluate the safety profile of MDI-2268, specifically its effect on bleeding time.
  • To compare the efficacy of MDI-2268 with enoxaparin, a standard anticoagulant.

Main Methods:

  • An electrolytic injury model of VT was established in C57BL/6 mice.
  • Mice were treated with different doses of MDI-2268, enoxaparin, or a combination.
  • Thrombus weight and tail bleeding time were measured on Day 2 post-injury.

Main Results:

  • MDI-2268 demonstrated a dose-dependent reduction in thrombus weight.
  • Both MDI-2268 (3 mg/kg) and enoxaparin significantly reduced thrombus weight compared to controls.
  • MDI-2268 did not significantly prolong tail bleeding time at the tested doses.

Conclusions:

  • MDI-2268 is a novel pro-fibrinolytic agent with potent antithrombotic activity.
  • MDI-2268 shows a favorable safety profile, with no significant increase in bleeding time.
  • MDI-2268 represents a promising therapeutic candidate for managing acute venous thrombosis.
Keywords:
PAI-1inhibitorplasminogenvenous thrombosis

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