ArticleScience translational medicine2014
Optimizing human apyrase to treat arterial thrombosis and limit reperfusion injury without increasing bleeding risk.
Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Safety, Tolerability, and Pharmacodynamics of AZD3366 (Optimized Human CD39L3 Apyrase) Alone and in Combination With Ticagrelor and Acetylsalicylic Acid: A Phase 1, Randomized, Placebo-Controlled Study.Journal of the American Heart Association · 2024Trial
- Structural Modeling of NTPDase-Substrate Complexes Preserving Catalytic Experimental Features.ACS omega · 2025Article
- Targeting the CD39/CD73 pathway: New insights into cardiac fibrosis and inflammation in female cardiac surgery patients.Journal of molecular and cellular cardiology plus · 2025Article
- Heterologous expression and biochemical characterization of the recombinant nucleoside triphosphate diphosphohydrolase 2 (LbNTPDase2) from Leishmania (Viannia) braziliensis.Purinergic signalling · 2024Article
- Exploring the Role of Platelets in Virus-Induced Inflammatory Demyelinating Disease and Myocarditis.International journal of molecular sciences · 2024Article
- Article
- Dysfunctional Immune Regulation in Autoimmune Hepatitis: From Pathogenesis to Novel Therapies.Frontiers in immunology · 2021Review
- Molecular Drivers of Platelet Activation: Unraveling Novel Targets for Anti-Thrombotic and Anti-Thrombo-Inflammatory Therapy.International journal of molecular sciences · 2020Review
- Modulation of CD39 and Exogenous APT102 Correct Immune Dysfunction in Experimental Colitis and Crohn's Disease.Journal of Crohn's & colitis · 2020Article
- Human Recombinant Apyrase Therapy Protects Against Myocardial Ischemia/Reperfusion Injury and Preserves Left Ventricular Systolic Function in Rats, as Evaluated by 7T Cardiovascular Magnetic Resonance Imaging.Korean journal of radiology · 2020Article
- Adenosine Metabolism: Emerging Concepts for Cancer Therapy.Cancer cell · 2019Review
- Quantitative dynamics of reversible platelet aggregation: mathematical modelling and experiments.Scientific reports · 2019Article
- Platelet biology and functions: new concepts and clinical perspectives.Nature reviews. Cardiology · 2019Review
- CD39-adenosinergic axis in renal pathophysiology and therapeutics.Purinergic signalling · 2018Review
- Loss of vascular expression of nucleoside triphosphate diphosphohydrolase-1/CD39 in hypertension.Purinergic signalling · 2018Article
- A non-contrast CMR index for assessing myocardial fibrosis.Magnetic resonance imaging · 2017Article
- Hyperthermia and associated changes in membrane fluidity potentiate P2X7 activation to promote tumor cell death.Oncotarget · 2017Article
- Recombinant soluble apyrase APT102 inhibits thrombosis and intimal hyperplasia in vein grafts without adversely affecting hemostasis or re-endothelialization.Journal of thrombosis and haemostasis : JTH · 2017Article
- Deregulation of ocular nucleotide homeostasis in patients with diabetic retinopathy.Journal of molecular medicine (Berlin, Germany) · 2017Article
- Glaucocalyxin A Ameliorates Myocardial Ischemia-Reperfusion Injury in Mice by Suppression of Microvascular Thrombosis.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
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10 authors at 2 institutions in 1 country.
Funding
Abstract
In patients with acute myocardial infarction undergoing reperfusion therapy to restore blood flow through blocked arteries, simultaneous inhibition of platelet P2Y12 receptors with the current standard of care neither completely prevents recurrent thrombosis nor provides satisfactory protection against reperfusion injury. Additionally, these antiplatelet drugs increase the risk of bleeding. To devise a different strategy, we engineered and optimized the apyrase activity of human nucleoside triphosphate diphosphohydrolase-3 (CD39L3) to enhance scavenging of extracellular adenosine diphosphate, a predominant ligand of P2Y12 receptors. The resulting recombinant protein, APT102, exhibited greater than four times higher adenosine diphosphatase activity and a 50 times longer plasma half-life than did native apyrase. Treatment with APT102 before coronary fibrinolysis with intravenous recombinant human tissue-type plasminogen activator in conscious dogs completely prevented thrombotic reocclusion and significantly decreased infarction size by 81% without increasing bleeding time. In contrast, clopidogrel did not prevent coronary reocclusion and increased bleeding time. In a murine model of myocardial reperfusion injury caused by transient coronary artery occlusion, APT102 also decreased infarct size by 51%, whereas clopidogrel was not effective. These preclinical data suggest that APT102 should be tested for its ability to safely and effectively maximize the benefits of myocardial reperfusion therapy in patients with arterial thrombosis.
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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.