PAI-1 Inhibitors for Health & Longevity - Quick Reference Sheet

PAI-1 Inhibitors for Health & Longevity

Created on 09/01/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 5 Audit

These oral medications block the body's main brake on clot dissolution. Longevity interest rests on a family that makes half the normal amount from birth and lives longer, plus mouse work. Human results are narrow: two small cancer studies and one ageing study, all without comparison groups, almost all from the compound's owners. None is approved anywhere. (Full Review)

Protocol

No approved protocol exists
Registered trials only
No PAI-1 inhibitor is licensed anywhere; every regimen below is one used by investigators inside registered trials.
Standard trial regimen
120–150 mg once daily
TM5614 orally for the first four to eight weeks, escalated to 180 mg once daily thereafter.
Best time of day
Evening
PAI-1 peaks in the early morning; trials dosed in the evening, positioning drug exposure against that peak.
Time to effect
Molecular response
12 months
Assessed in leukaemia.
Tumour response
8 weeks
Assessed in melanoma.
Oxygen requirement
3–5 days
Assessed in pneumonia. Nothing gives a timeline for a longevity endpoint.

Benefits

Contraindications
  • Active clinically significant bleeding of any site
  • Known bleeding disorder, including complete PAI-1 deficiency and haemophilia
  • Platelet count below 50 × 10⁹/L or haematocrit below 30%
  • Any history of stroke, brain tumour, arteriovenous malformation or aneurysm
  • Surgery or trauma involving the brain or spinal cord within 90 days
  • Severe uncontrolled hypertension (systolic above 200 mmHg beyond 12 hours)
  • Concurrent full-dose anticoagulation
  • Liver impairment of Child-Pugh Class B or C (moderate to severe), or liver enzymes above the upper limit of normal
  • Pregnancy and breastfeeding
  • Active venous thromboembolic disease under treatment
  • Thrombolytic agents (alteplase, tenecteplase)
Key Interactions
  • Antiplatelet medications (aspirin, clopidogrel, ticagrelor, prasugrel)
  • Over-the-counter analgesics (aspirin, ibuprofen, naproxen, diclofenac)
  • Immune checkpoint inhibitors (nivolumab, pembrolizumab)
  • Tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib)
  • Medications that also lower PAI-1 (ramipril, losartan, atorvastatin, fenofibrate, metformin)
  • Supplements with fibrinolytic or antiplatelet activity (nattokinase, lumbrokinase, serrapeptase, high-dose fish oil, high-dose vitamin E, garlic, ginkgo, curcumin, bromelain)
  • Other interventions (elective surgery, dental extraction, colonoscopy with biopsy, cosmetic procedures)

Risk & Side Effects

  • Medium: Drug-related liver injury
  • Low: Bleeding from unopposed clot breakdown
  • Speculative: Impaired wound healing and post-surgical repair; context-dependent tumour promotion; disturbed phosphate and mineral regulation; unmasking of latent autoimmunity

Monitoring

Marker Target Why
PAI-1 activity Below 10 IU/mL Direct target engagement
PAI-1 antigen Below 20 ng/mL Total protein pool, active plus latent
Platelet count and haemoglobin Platelets 150–400 × 10⁹/L; haemoglobin mid-reference for sex Detects bleeding before it is visible
Prothrombin time with INR, and activated partial thromboplastin time Within laboratory reference range Baseline clotting competence
D-dimer Below 0.5 mg/L fibrinogen-equivalent units Rises when clot breakdown accelerates
Fibrinogen 200–300 mg/dL Falling values suggest excessive fibrinolysis
Alanine and aspartate aminotransferase, bilirubin Alanine aminotransferase below 25 U/L in men and 20 U/L in women Detects the one adverse event attributed to this drug class
Fasting insulin and HOMA-IR Insulin below 5 µIU/mL; HOMA-IR below 1.5 The metabolic axis linked to low PAI-1 in carriers
High-sensitivity C-reactive protein Below 1.0 mg/L Inflammation is the main upstream driver of PAI-1
eGFR Above 90 mL/min/1.73 m² Clearance route is unpublished, so kidney function is tracked as a precaution

Cadence: Baseline, one week, four weeks, eight weeks, then every three months while treatment continues; tightening to weekly if any bleeding symptom or liver enzyme rise appears.

Qualitative Assessment

  • Easy bruising, gum bleeding when brushing, or nosebleeds lasting beyond ten minutes
  • Menstrual volume and cycle timing in women of reproductive age
  • Time for small cuts and dental sites to stop bleeding and to close
  • Energy levels and exercise tolerance
  • Cognitive clarity and sleep quality, both of which shift with the inflammatory state that drives PAI-1