ArticleProceedings of the National Academy of Sciences of the United States of America2013
Mechanistic characterization and crystal structure of a small molecule inactivator bound to plasminogen activator inhibitor-1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Assays to quantify fibrinolysis: strengths and limitations. Communication from the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee on fibrinolysis.Journal of thrombosis and haemostasis : JTH · 2023Guideline
- PAI-1: A Key Signal at the Crossroads of Stem Cell Differentiation and Senescence.International journal of molecular sciences · 2025Review
- A signaling pathway map of plasminogen activator inhibitor-1 (PAI-1/SERPINE-1): a review of an innovative frontier in molecular aging and cellular senescence.Cell communication and signaling : CCS · 2024Review
- Deep mutational scanning and massively parallel kinetics of plasminogen activator inhibitor-1 functional stability to probe its latency transition.The Journal of biological chemistry · 2022Article
- Innovative Non-PrP-Targeted Drug Strategy Designed to Enhance Prion Clearance.Journal of medicinal chemistry · 2022Article
- Neuroserpin: structure, function, physiology and pathology.Cellular and molecular life sciences : CMLS · 2021Review
- A Narrative Review on Plasminogen Activator Inhibitor-1 and Its (Patho)Physiological Role: To Target or Not to Target?International journal of molecular sciences · 2021Review
- Structural Insight into the Two-Step Mechanism of PAI-1 Inhibition by Small Molecule TM5484.International journal of molecular sciences · 2021Article
- An aberrant STAT pathway is central to COVID-19.Cell death and differentiation · 2020Review
- Structural Insights into the Mechanism of a Nanobody That Stabilizes PAI-1 and Modulates Its Activity.International journal of molecular sciences · 2020Article
- Plasminogen activation in the musculoskeletal acute phase response: Injury, repair, and disease.Research and practice in thrombosis and haemostasis · 2020Review
- Molecular mechanism of two nanobodies that inhibit PAI-1 activity reveals a modulation at distinct stages of the PAI-1/plasminogen activator interaction.Journal of thrombosis and haemostasis : JTH · 2020Article
- High-affinity binding of plasminogen-activator inhibitor 1 complexes to LDL receptor-related protein 1 requires lysines 80, 88, and 207.The Journal of biological chemistry · 2020Article
- Targeting PAI-1 in Cardiovascular Disease: Structural Insights Into PAI-1 Functionality and Inhibition.Frontiers in cardiovascular medicine · 2020Review
- Discovery and characterisation of an antibody that selectively modulates the inhibitory activity of plasminogen activator inhibitor-1.Scientific reports · 2019Article
- Dual-reporter high-throughput screen for small-moleculeThe Journal of biological chemistry · 2019Article
- 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
- Serpin latency transition at atomic resolution.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Plasminogen activator inhibitor type-1 (PAI-1) is a member of the serine protease inhibitor (serpin) family. Excessive PAI-1 activity is associated with human disease, making it an attractive pharmaceutical target. However, like other serpins, PAI-1 has a labile structure, making it a difficult target for the development of small molecule inhibitors, and to date, there are no US Food and Drug Administration-approved small molecule inactivators of any serpins. Here we describe the mechanistic and structural characterization of a high affinity inactivator of PAI-1. This molecule binds to PAI-1 reversibly and acts through an allosteric mechanism that inhibits PAI-1 binding to proteases and to its cofactor vitronectin. The binding site is identified by X-ray crystallography and mutagenesis as a pocket at the interface of β-sheets B and C and α-helix H. A similar pocket is present on other serpins, suggesting that this site could be a common target in this structurally conserved protein family.
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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.