ArticleThe Journal of clinical investigation2016
A chimeric platelet-targeted urokinase prodrug selectively blocks new thrombus formation.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 32 citations in OpenAlex.
- Engineering platelets as cancer therapeutics.Nature reviews. Clinical oncology · 2026Review
- Packaging of supplemented urokinase into alpha granules of in vitro-grown megakaryocytes for targeted nascent clot lysis.Blood advances · 2024Article
- Engineered platelets-based drug delivery platform for targeted thrombolysis.Acta pharmaceutica Sinica. B · 2022Article
- Visualizing thrombosis to improve thrombus resolution.Research and practice in thrombosis and haemostasis · 2021Article
- Bivalent engagement of endothelial surface antigens is critical to prolonged surface targeting and protein delivery in vivo.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Vascular Nanomedicine: Current Status, Opportunities, and Challenges.Seminars in thrombosis and hemostasis · 2020Review
- Structure-guided design of pure orthosteric inhibitors of αIIbβ3 that prevent thrombosis but preserve hemostasis.Nature communications · 2020Article
- Recent strategies on targeted delivery of thrombolytics.Asian journal of pharmaceutical sciences · 2019Review
- Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting.Journal of hematology & oncology · 2019Review
- Anti-platelet drugs and their necessary interaction with endothelial mediators and platelet cyclic nucleotides for therapeutic efficacy.Pharmacology & therapeutics · 2019Review
- Platelets Can Soak It Up and Then Spit It Out.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Platelet-targeted dual pathway antithrombotic inhibits thrombosis with preserved hemostasis.JCI insight · 2018Article
- ICAM-1-targeted thrombomodulin mitigates tissue factor-driven inflammatory thrombosis in a human endothelialized microfluidic model.Blood advances · 2017Article
- Platelet microparticle-inspired clot-responsive nanomedicine for targeted fibrinolysis.Biomaterials · 2017Article
- Novel Thrombolytic Drug Based on Thrombin Cleavable Microplasminogen Coupled to a Single-Chain Antibody Specific for Activated GPIIb/IIIa.Journal of the American Heart Association · 2017Article
- Platelets and platelet adhesion molecules: novel mechanisms of thrombosis and anti-thrombotic therapies.Thrombosis journal · 2016Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
The use of fibrinolytic agents to prevent new thrombus formation is limited by an increased risk of bleeding due to lysis of hemostatic clots that prevent hemorrhage in damaged blood vessels. We sought to develop an agent that provides thromboprophylaxis without carrying a significant risk of causing systemic fibrinolysis or disrupting hemostatic clots. We previously showed that platelet (PLT) α granule-delivered urokinase plasminogen activator (uPA) is highly effective in preventing thrombosis, while being associated with little systemic fibrinolysis or bleeding. Here, we generated a chimeric prodrug composed of a single-chain version of the variable region of an anti-αIIbβ3 mAb fused to a thrombin-activatable, low-molecular-weight pro-uPA (PLT/uPA-T). PLT/uPA-T recognizes human αIIbβ3 on both quiescent and activated platelets and is enzymatically activated specifically by thrombin. We found that this prodrug binds tightly to human platelets even after gel filtration, has a prolonged half-life in mice transgenic for human αIIb compared with that of uPA-T, and prevents clot formation in a microfluidic system. Importantly, in two murine injury models, PLT/uPA-T did not lyse preexisting clots, even when administration was delayed by as little as 10 minutes, while it concurrently prevented the development of nascent thrombi. Thus, PLT/uPA-T represents the prototype of a platelet-targeted thromboprophylactic agent that selectively targets nascent over preexisting thrombi.
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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.