ArticleBiochemical pharmacology2004
Antiaggregatory activity in human platelets of potent antagonists of the P2Y 1 receptor.
Article in Biochemical pharmacology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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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.
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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
45 citing papers in PubMed, 97 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
- Residue Interaction Network Reveals Allosteric Pathways Linking Orthosteric and Intracellular Sites in Class A GPCRs.Journal of chemical information and modeling · 2026Article
- Article
- Design and Pharmacological Characterization of a Novel Antithrombotic P2YInternational journal of molecular sciences · 2025Article
- Selective Inhibition of P2YCNS neuroscience & therapeutics · 2024Article
- Exploring bias in platelet P2YBritish journal of pharmacology · 2024Review
- Personalized Dual Antiplatelet Therapy in Acute Coronary Syndromes: Striking a Balance Between Bleeding and Thrombosis.Current cardiology reports · 2023Review
- Pharmacological Profile of the Purinergic P2Y Receptors That Modulate, in Response to ADPβS, the Vasodepressor Sensory CGRPergic Outflow in Pithed Rats.Pharmaceuticals (Basel, Switzerland) · 2023Article
- The P2YCellular and molecular life sciences : CMLS · 2022Article
- Nucleotide P2YPurinergic signalling · 2020Article
- The role of purinergic P2YPurinergic signalling · 2020Article
- Overview of Biologically Active Nucleoside Phosphonates.Frontiers in chemistry · 2020Review
- Precision medicine in COPD: where are we and where do we need to go?European respiratory review : an official journal of the European Respiratory Society · 2018Review
- The P2Y1 receptor antagonist MRS2500 prevents carotid artery thrombosis in cynomolgus monkeys.Journal of thrombosis and thrombolysis · 2016Article
- Blood cells: an historical account of the roles of purinergic signalling.Purinergic signalling · 2015Review
- Expression and function of P2 receptors in hematopoietic stem and progenitor cells.Stem cell investigation · 2015Review
- ADP-induced bladder contractility is mediated by P2Y12 receptor and temporally regulated by ectonucleotidases and adenosine signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- Purinergic neuromuscular transmission in the gastrointestinal tract; functional basis for future clinical and pharmacological studies.British journal of pharmacology · 2014Review
- P2Y₁ and P2Y₁₂ receptors in hypoxia- and adenosine diphosphate-induced pulmonary vasoconstriction in vivo in the pig.European journal of applied physiology · 2014Article
- Purinergic inhibitory regulation of murine detrusor muscles mediated by PDGFRα+ interstitial cells.The Journal of physiology · 2014Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Activation of the P2Y(1) nucleotide receptor in platelets by ADP causes changes in shape and aggregation, mediated by activation of phospholipase C (PLC). Recently, MRS2500(2-iodo-N(6)-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate) was introduced as a highly potent and selective antagonist for this receptor. We have studied the actions of MRS2500 in human platelets and compared these effects with the effects of two acyclic nucleotide analogues, a bisphosphate MRS2298 and a bisphosphonate derivative MRS2496, which act as P2Y(1) receptor antagonists, although less potently than MRS2500. Improved synthetic methods for MRS2500 and MRS2496 were devised. The bisphosphonate is predicted to be more stable in general in biological systems than phosphate antagonists due to the non-hydrolyzable CP bond. MRS2500 inhibited the ADP-induced aggregation of human platelets with an IC(50) value of 0.95 nM. MRS2298 and MRS2496 also both inhibited the ADP-induced aggregation of human platelets with IC(50) values of 62.8 nM and 1.5 microM, respectively. A similar order of potency was observed for the three antagonists in binding to the recombinant human P2Y(1) receptor and in inhibition of ADP-induced shape change and ADP-induced rise in intracellular Ca(2+). No substantial antagonism of the pathway linked to the inhibition of cyclic AMP was observed for the nucleotide derivatives, indicating no interaction of these three P2Y(1) receptor antagonists with the proaggregatory P2Y(12) receptor, which is also activated by ADP. Thus, all three of the bisphosphate derivatives are highly selective antagonists of the platelet P2Y(1) receptor, and MRS2500 is the most potent such antagonist yet reported.
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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.