ArticleThe Journal of biological chemistry2010
Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
- A potent inhibitor of PAI-1, MDI-2517, mitigates disease severity in a preclinical systemic sclerosis model.JCI insight · 2026Article
- Heterogeneity and interplay: the multifaceted role of cancer-associated fibroblasts in the tumor and therapeutic strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- Plant-Derived Compounds and Extracts as Modulators of Plasmin Activity-A Review.Molecules (Basel, Switzerland) · 2023Review
- Circadian rhythm of plasminogen activator inhibitor-1 and cardiovascular complications in type 2 diabetes.Frontiers in endocrinology · 2023Review
- Innovative Non-PrP-Targeted Drug Strategy Designed to Enhance Prion Clearance.Journal of medicinal chemistry · 2022Article
- PAI-1 in Diabetes: Pathophysiology and Role as a Therapeutic Target.International journal of molecular sciences · 2021Review
- Targeting PAI-1 in Cardiovascular Disease: Structural Insights Into PAI-1 Functionality and Inhibition.Frontiers in cardiovascular medicine · 2020Review
- Dual-reporter high-throughput screen for small-moleculeThe Journal of biological chemistry · 2019Article
- Serpine1 Knockdown Enhances MMP Activity after Flexor Tendon Injury in Mice: Implications for Adhesions Therapy.Scientific reports · 2018Article
- Characterization of the Annonaceous acetogenin, annonacinone, a natural product inhibitor of plasminogen activator inhibitor-1.Scientific reports · 2016Article
- A specific plasminogen activator inhibitor-1 antagonist derived from inactivated urokinase.Journal of cellular and molecular medicine · 2016Article
- Plasminogen Activator Inhibitor-1 in Cancer: Rationale and Insight for Future Therapeutic Testing.Cancer research · 2015Review
- Chemical Antagonists of Plasminogen Activator Inhibitor-1: Mechanisms of Action and Therapeutic Potential in Vascular Disease.Journal of molecular and genetic medicine : an international journal of biomedical research · 2014Article
- Mechanistic characterization and crystal structure of a small molecule inactivator bound to plasminogen activator inhibitor-1.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Characterization of a small molecule inhibitor of plasminogen activator inhibitor type 1 that accelerates the transition into the latent conformation.The Journal of biological chemistry · 2013Article
- uPA binding to PAI-1 induces corneal myofibroblast differentiation on vitronectin.Investigative ophthalmology & visual science · 2012Article
- ARNTL2 and SERPINE1: potential biomarkers for tumor aggressiveness in colorectal cancer.Journal of cancer research and clinical oncology · 2012Article
- Effects of altered plasminogen activator inhibitor-1 expression on cardiovascular disease.Current drug targets · 2011Review
- Novel bis-arylsulfonamides and aryl sulfonimides as inactivators of plasminogen activator inhibitor-1 (PAI-1).Bioorganic & medicinal chemistry letters · 2010Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Plasminogen activator inhibitor type 1, (PAI-1) the primary inhibitor of the tissue-type (tPA) and urokinase-type (uPA) plasminogen activators, has been implicated in a wide range of pathological processes, making it an attractive target for pharmacologic inhibition. Currently available small-molecule inhibitors of PAI-1 bind with relatively low affinity and do not inactivate PAI-1 in the presence of its cofactor, vitronectin. To search for novel PAI-1 inhibitors with improved potencies and new mechanisms of action, we screened a library selected to provide a range of biological activities and structural diversity. Five potential PAI-1 inhibitors were identified, and all were polyphenolic compounds including two related, naturally occurring plant polyphenols that were structurally similar to compounds previously shown to provide cardiovascular benefit in vivo. Unique second generation compounds were synthesized and characterized, and several showed IC(50) values for PAI-1 between 10 and 200 nm. This represents an enhanced potency of 10-1000-fold over previously reported PAI-1 inactivators. Inhibition of PAI-1 by these compounds was reversible, and their primary mechanism of action was to block the initial association of PAI-1 with a protease. Consistent with this mechanism and in contrast to previously described PAI-1 inactivators, these compounds inactivate PAI-1 in the presence of vitronectin. Two of the compounds showed efficacy in ex vivo plasma and one blocked PAI-1 activity in vivo in mice. These data describe a novel family of high affinity PAI-1-inactivating compounds with improved characteristics and in vivo efficacy, and suggest that the known cardiovascular benefits of dietary polyphenols may derive in part from their inactivation of PAI-1.
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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 OpenQuestion graph.