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Published on: May 24, 2024
PAI-1 as a Therapeutic Target: A State-of-the-Art Review
Jacob Wortley1, Lily Crone1, Neha Soogoor1
1Texas Christian University Anne Burnett Marion School of Medicine, Department of Medicine, Texas, United States, Fort Worth.
Abstract:
Plasminogen activator inhibitor (PAI-1) is a member of the serine protease inhibitor family critical in regulating fibrinolysis and is associated with diverse pathologies including cardiovascular disease, metabolic disorders, cancer, aging, and many others. Despite its clinical significance and extensive research, there are as of yet still no FDA- or EMA-approved therapeutics that specifically target PAI-1. This review examines therapeutic strategies including small molecules, RNA aptamers, monoclonal antibodies, and repurposed pharmaceuticals. Notable challenges in the development of these therapies include the interplay of PAI-1 with tissue-specific mediators such as vitronectin and the multi-dimensional, tissue-specific effects of PAI-1 modulation. Promising approaches will require tissue- and temporal expression-based interventions. Further characterization of PAI-1's structural dynamics and its role in various disease processes will shape its potential as a therapeutic target across broad fields in medicine.
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