ArticleScientific reports2019
Discovery and characterisation of an antibody that selectively modulates the inhibitory activity of plasminogen activator inhibitor-1.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Review
- Targeting autophagy and plasminogen activator inhibitor-1 increases survival and remodels the tumor microenvironment in glioblastoma.Journal of experimental & clinical cancer research : CR · 2025Article
- 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
- Targeting Fibrinolytic Inhibition for Venous Thromboembolism Treatment: Overview of an Emerging Therapeutic Approach.Circulation · 2024Review
- Inter-Organ Communication Involved in Brown Adipose Tissue Thermogenesis.Advances in experimental medicine and biology · 2024Review
- Plasminogen activator inhibitor 1 is not a major causative factor for exacerbation in a mouse model of SARS-CoV-2 infection.Scientific reports · 2023Article
- Circadian rhythm of plasminogen activator inhibitor-1 and cardiovascular complications in type 2 diabetes.Frontiers in endocrinology · 2023Review
- "Super" SERPINs-A stabilizing force against fibrinolysis in thromboinflammatory conditions.Frontiers in cardiovascular medicine · 2023Review
- The role of CDH2 and MCP-1 mRNAs of blood extracellular vesicles in predicting early-stage diabetic nephropathy.PloS one · 2022Article
- Endogenous fibrinolysis inhibitors in acute coronary syndrome.American heart journal plus : cardiology research and practice · 2021Review
- Therapeutic Potential of Targeting Plasminogen Activator Inhibitor-1 in COVID-19.Trends in pharmacological sciences · 2021Article
- PAI-1 in Diabetes: Pathophysiology and Role as a Therapeutic Target.International journal of molecular sciences · 2021Review
- A Serpin With a Finger in Many PAIs: PAI-1's Central Function in Thromboinflammation and Cardiovascular Disease.Frontiers in cardiovascular medicine · 2021Review
- Structural Insights into the Mechanism of a Nanobody That Stabilizes PAI-1 and Modulates Its Activity.International journal of molecular sciences · 2020Article
- 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
- Targeting PAI-1 in Cardiovascular Disease: Structural Insights Into PAI-1 Functionality and Inhibition.Frontiers in cardiovascular medicine · 2020Review
- Article
- The Role of Metabolic Syndrome in Endometrial Cancer: A Review.Frontiers in oncology · 2019Review
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor (serpin) that regulates fibrinolysis, cell adhesion and cell motility via its interactions with plasminogen activators and vitronectin. PAI-1 has been shown to play a role in a number of diverse pathologies including cardiovascular diseases, obesity and cancer and is therefore an attractive therapeutic target. However the multiple patho-physiological roles of PAI-1, and understanding the relative contributions of these in any one disease setting, make the development of therapeutically relevant molecules challenging. Here we describe the identification and characterisation of fully human antibody MEDI-579, which binds with high affinity and specificity to the active form of human PAI-1. MEDI-579 specifically inhibits serine protease interactions with PAI-1 while conserving vitronectin binding. Crystallographic analysis reveals that this specificity is achieved through direct binding of MEDI-579 Fab to the reactive centre loop (RCL) of PAI-1 and at the same exosite used by both tissue and urokinase plasminogen activators (tPA and uPA). We propose that MEDI-579 acts by directly competing with proteases for RCL binding and as such is able to modulate the interaction of PAI-1 with tPA and uPA in a way not previously described for a human PAI-1 inhibitor.
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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.