ArticleJournal of thrombosis and thrombolysis2016
The P2Y1 receptor antagonist MRS2500 prevents carotid artery thrombosis in cynomolgus monkeys.
Article in Journal of thrombosis and thrombolysis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- Advances in nucleotide-based P2Y₁ antagonism: implications for cardiovascular therapeutics.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Article
- Novel Aspects Targeting Platelets in Atherosclerotic Cardiovascular Disease-A Translational Perspective.International journal of molecular sciences · 2023Review
- Involvement of purinergic P2Y1R in antidepressant-like effects of electroacupuncture treatment on social isolation stress mice.Purinergic signalling · 2023Article
- Novel strategies in antithrombotic therapy: targeting thrombosis while preserving hemostasis.Frontiers in cardiovascular medicine · 2023Review
- Novel Antithrombotic Agents in Ischemic Cardiovascular Disease: Progress in the Search for the Optimal Treatment.Journal of cardiovascular development and disease · 2022Review
- Current and Novel Antiplatelet Therapies for the Treatment of Cardiovascular Diseases.International journal of molecular sciences · 2021Review
- Improved efficacy/safety profile of factor XIa inhibitor BMS-724296 versus factor Xa inhibitor apixaban and thrombin inhibitor dabigatran in cynomolgus monkeys.Research and practice in thrombosis and haemostasis · 2021Article
- Nucleotide P2YPurinergic signalling · 2020Article
- Purinergic Signaling: Impact of GPCR Structures on Rational Drug Design.ChemMedChem · 2020Review
- Synthesis and preclinical validation of novel P2Y1 receptor ligands as a potent anti-prostate cancer agent.Scientific reports · 2019Article
- Novel Antiplatelet Therapies for Atherothrombotic Diseases.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
- Platelets as Modulators of Cerebral Ischemia/Reperfusion Injury.Frontiers in immunology · 2019Review
- Breakthrough in GPCR Crystallography and Its Impact on Computer-Aided Drug Design.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Demystifying P2YJournal of chemical information and modeling · 2017Article
- Ligand binding to a G protein-coupled receptor captured in a mass spectrometer.Science advances · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adenosine diphosphate directly induces platelet aggregation via the G-protein coupled P2Y1 and P2Y12 receptors. P2Y12, but not P2Y1, receptor antagonists are available in the clinic. The relevance of the P2Y1 receptor as an antiplatelet target has been studied in rodents, but not in higher species. We therefore examined effects of the pharmacological blockade of the P2Y1 receptor with its selective antagonist MRS2500 in monkey models of electrolytic-mediated arterial thrombosis (ECAT) and kidney bleeding time (KBT). Abciximab, a GPIIb-IIIa antagonist, and cangrelor, a P2Y12 antagonist, were utilized to validate these monkey models. Compounds were given IV at 15-60 min before thrombosis initiation in anesthetized monkeys. Scanning electron microscopy showed the luminal surface of thrombotic artery covered with platelet aggregates and fibrin network. Administration of abciximab at 0.25 and 0.7 mg/kg IV significantly reduced thrombus weight by 71 ± 1 and 100 ± 0 %, and increased KBT by 10.0 ± 0.1- and 10.1 ± 0-fold, respectively (n = 3/dose). Likewise, cangrelor at 0.6 and 2 mg/kg/h IV significantly reduced thrombus weight significantly by 72 ± 9 % and 100 ± 0 % and increased KBT by 2.1 ± 0.1- and 9.8 ± 0.2-fold, respectively (n = 3/dose). MRS2500 [mg/kg + mg/kg/h IV] at 0.09 + 0.14 and 0.45 + 0.68 significantly reduced thrombus weight by 57 ± 1 % and 88 ± 1 % and increased KBT by 2.1 ± 0.3- and 4.9 ± 0.6-fold, respectively (n = 4/dose). In summary, MRS2500 prevented occlusive arterial thrombosis at a dose that moderately prolonged KBT, indicating a role of P2Y1 receptors in arterial thrombosis and hemostasis in monkeys. Thus P2Y1 receptor antagonism provides a suitable target for drug discovery.
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