ReviewCells2026
Plasminogen Activator Inhibitor-1 as a Therapeutic Target for Healthy Longevity, Immunosenescence, and Age-Related Disease: Translational Development of the Small-Molecule Inhibitor TM5614.
Review in Cells, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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0 citing papers in PubMed.
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Authors and funding
2 authors.
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Abstract
Plasminogen activator inhibitor-1 (PAI-1), encoded by SERPINE1, is the principal physiological inhibitor of tissue-type and urokinase-type plasminogen activators and a central regulator of fibrinolysis. Beyond its canonical hemostatic role, PAI-1 has emerged as a pleiotropic mediator of tissue remodeling, fibrosis, metabolic dysfunction, cancer progression, cellular senescence, and age-associated immune dysregulation. A central argument of this review is that PAI-1 should be understood not only as a downstream biomarker of aging-associated pathology, but also as an active effector linking senescence-associated secretory phenotype (SASP) signaling, chronic low-grade inflammation, impaired immune surveillance, fibrotic extracellular matrix remodeling, and a prothrombotic state. In this framework, PAI-1 may function as an immune-aging checkpoint: a molecular node through which senescent, stromal, malignant, and inflammatory cells reinforce immune evasion and tissue dysfunction. Structure-guided drug discovery has enabled the development of small-molecule PAI-1 inhibitors, including TM5275, TM5441, TM5509, and TM5614. Among these, TM5614 is an orally available investigational compound that has progressed to clinical evaluation. Preclinical studies support anti-thrombotic, anti-fibrotic, anti-inflammatory, anti-senescent, and tumor-microenvironment-modulating effects of PAI-1 inhibition, while early clinical studies have evaluated TM5614 in chronic myeloid leukemia, immune-checkpoint-refractory malignant melanoma, non-small-cell lung cancer, and COVID-19-associated pneumonia. This review summarizes the biology of PAI-1, expands the discussion of immunoaging, reviews representative preclinical and clinical data, compares available PAI-1 inhibitors, and discusses the translational opportunities and safety considerations for TM5614 and related compounds.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.