Evidence map›Paper›PMID 26743169›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2016

Synergistic Inhibition of Both P2Y1 and P2Y12 Adenosine Diphosphate Receptors As Novel Approach to Rapidly Attenuate Platelet-Mediated Thrombosis.

Thomas Gremmel, Ivan B Yanachkov, Milka I Yanachkova, George E Wright, Joseph Wider, Vishnu V R Undyala, Alan D Michelson, Andrew L Frelinger, Karin Przyklenk

Open access · bronzeAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.9field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 55 citations in OpenAlex.

  1. From danger to resolution: targeting purinergic signaling in CNS diseases.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
    Review
  2. 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 · 2026
    Review
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  9. Platelet P2YBMC biology · 2023
    Article
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  16. Article
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  19. Role of P2Y Receptors in Platelet Extracellular Vesicle Release.International journal of molecular sciences · 2020
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Thomas GremmelFrom the Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (T.G., A.D.M., A.L.F.); Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (T.G.); GLSynthesis Inc, Worcester, MA (I.B.Y., M.I.Y., G.E.W.); and Cardiovascular Research Institute and Departments of Physiology and Emergency Medicine, Wayne State University School of Medicine, Detroit, MI (J.W., V.V.R.U., K.P.). thomas.gremmel@meduniwien.ac.at.
Ivan B YanachkovFrom the Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (T.G., A.D.M., A.L.F.); Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (T.G.); GLSynthesis Inc, Worcester, MA (I.B.Y., M.I.Y., G.E.W.); and Cardiovascular Research Institute and Departments of Physiology and Emergency Medicine, Wayne State University School of Medicine, Detroit, MI (J.W., V.V.R.U., K.P.).
Milka I YanachkovaFrom the Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (T.G., A.D.M., A.L.F.); Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (T.G.); GLSynthesis Inc, Worcester, MA (I.B.Y., M.I.Y., G.E.W.); and Cardiovascular Research Institute and Departments of Physiology and Emergency Medicine, Wayne State University School of Medicine, Detroit, MI (J.W., V.V.R.U., K.P.).
George E WrightFrom the Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (T.G., A.D.M., A.L.F.); Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (T.G.); GLSynthesis Inc, Worcester, MA (I.B.Y., M.I.Y., G.E.W.); and Cardiovascular Research Institute and Departments of Physiology and Emergency Medicine, Wayne State University School of Medicine, Detroit, MI (J.W., V.V.R.U., K.P.).
Joseph WiderFrom the Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (T.G., A.D.M., A.L.F.); Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (T.G.); GLSynthesis Inc, Worcester, MA (I.B.Y., M.I.Y., G.E.W.); and Cardiovascular Research Institute and Departments of Physiology and Emergency Medicine, Wayne State University School of Medicine, Detroit, MI (J.W., V.V.R.U., K.P.).
Vishnu V R UndyalaFrom the Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (T.G., A.D.M., A.L.F.); Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (T.G.); GLSynthesis Inc, Worcester, MA (I.B.Y., M.I.Y., G.E.W.); and Cardiovascular Research Institute and Departments of Physiology and Emergency Medicine, Wayne State University School of Medicine, Detroit, MI (J.W., V.V.R.U., K.P.).
Alan D MichelsonFrom the Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (T.G., A.D.M., A.L.F.); Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (T.G.); GLSynthesis Inc, Worcester, MA (I.B.Y., M.I.Y., G.E.W.); and Cardiovascular Research Institute and Departments of Physiology and Emergency Medicine, Wayne State University School of Medicine, Detroit, MI (J.W., V.V.R.U., K.P.).
Andrew L FrelingerFrom the Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (T.G., A.D.M., A.L.F.); Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (T.G.); GLSynthesis Inc, Worcester, MA (I.B.Y., M.I.Y., G.E.W.); and Cardiovascular Research Institute and Departments of Physiology and Emergency Medicine, Wayne State University School of Medicine, Detroit, MI (J.W., V.V.R.U., K.P.).
Karin PrzyklenkFrom the Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (T.G., A.D.M., A.L.F.); Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (T.G.); GLSynthesis Inc, Worcester, MA (I.B.Y., M.I.Y., G.E.W.); and Cardiovascular Research Institute and Departments of Physiology and Emergency Medicine, Wayne State University School of Medicine, Detroit, MI (J.W., V.V.R.U., K.P.).
Glsynthesis · USMedical University of Vienna · AT

Funding

Novel Antithrombotic Diadenosine Tetraphosphate AnalogsR44TR000983 · NCATS · GLSYNTHESIS, INC. · PI YANACHKOV, IVAN B · 2013 to 2015
$3.4M
Preconditioning Improves Coronary PatencyR01HL072684 · NHLBI · WAYNE STATE UNIVERSITY · PI PRZYKLENK, KARIN · 2002 to 2012
$2.2M
Novel Antithrombotic Diadenosine Tetraphosphate AnalogsR44HL088828 · NHLBI · GLSYNTHESIS, INC. · PI YANACHKOV, IVAN B · 2009 to 2010
$1.5M
Novel Antithrombotic Diadenosine Tetraphosphate AnalogsR43HL088828 · NHLBI · GLSYNTHESIS, INC. · PI YANACHKOV, IVAN B · 2007 to 2007
$333k
NCATS NIH HHS R44 TR000983NCATS NIH HHS R44TR000983NHLBI NIH HHS R01 HL072684NHLBI NIH HHS R01HL072684NHLBI NIH HHS R43 HL088828NHLBI NIH HHS R44 HL088828NHLBI NIH HHS R44HL088828
6 · The paper itself

Abstract

objectiveUnlike currently approved adenosine diphosphate receptor antagonists, the new diadenosine tetraphosphate derivative GLS-409 targets not only P2Y12 but also the second human platelet adenosine diphosphate receptor P2Y1 and may, therefore, be a promising antiplatelet drug candidate. The current study is the first to investigate the in vivo antithrombotic effects of GLS-409. APPROACH AND

resultsWe studied (1) the in vivo effects of GLS-409 on agonist-stimulated platelet aggregation in anesthetized rats, (2) the antithrombotic activity of GLS-409 and the associated effect on the bleeding time in a canine model of platelet-mediated coronary artery thrombosis, and (3) the inhibition of agonist-stimulated platelet aggregation by GLS-409 versus selective P2Y1 and P2Y12 inhibition in vitro in samples from healthy human subjects before and 2 hours after aspirin intake. In vivo treatment with GLS-409 significantly inhibited adenosine diphosphate- and collagen-stimulated platelet aggregation in rats. Further, GLS-409 attenuated cyclic flow variation, that is, platelet-mediated thrombosis, in vivo in our canine model of unstable angina. The improvement in coronary patency was accompanied by a nonsignificant 30% increase in bleeding time. Of note, GLS-409 exerted its effects without affecting rat and canine hemodynamics. Finally, in vitro treatment with GLS-409 showed effects similar to that of cangrelor and the combination of cangrelor with the selective P2Y1 inhibitor MRS 2179 on agonist-stimulated platelet aggregation in human platelet-rich plasma and whole blood before and 2 hours after aspirin intake.

conclusionsSynergistic inhibition of both P2Y1 and P2Y12 adenosine diphosphate receptors by GLS-409 immediately attenuates platelet-mediated thrombosis and effectively blocks agonist-stimulated platelet aggregation irrespective of concomitant aspirin therapy.

Indexed as

Adenosine DiphosphateAdenosine MonophosphateAdultAnimalsAspirinBlood CoagulationBlood PlateletsCoronary ThrombosisDinucleoside PhosphatesDisease Models, AnimalDogsDose-Response Relationship, DrugFemaleFibrinolytic AgentsHumansMaleAdenosine DiphosphateAdenosine MonophosphateAspirincangrelorDinucleoside PhosphatesFibrinolytic AgentsN(6)-methyl-2'-deoxyadenosine 3',5'-diphosphateP2RY12 protein, humanP2ry12 protein, ratP2RY1 protein, humanP2ry1 protein, ratPlatelet Aggregation InhibitorsPurinergic P2Y Receptor AntagonistsReceptors, Purinergic P2Y1Receptors, Purinergic P2Y12adenosine diphosphateantiplatelet therapyaspirinP2Y1P2Y12

Identifiers

PMID26743169
PMCPMC4767596
OpenAlexW2228160834

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.