Evidence map›Paper›PMID 25147334›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2014

RUC-4: a novel αIIbβ3 antagonist for prehospital therapy of myocardial infarction.

Jihong Li, Spandana Vootukuri, Yi Shang, Ana Negri, Jian-Kang Jiang, Mark Nedelman, Thomas G Diacovo, Marta Filizola, Craig J Thomas, Barry S Coller

Open access · greenAbstract readComparative StudyVideo-Audio Media
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

49 citing papers in PubMed, 81 citations in OpenAlex.

  1. Trial
  2. Pharmacokinetics, pharmacodynamics, and tolerability of subcutaneous administration of a novel glycoprotein IIb/IIIa inhibitor, RUC-4, in patients with ST-segment elevation myocardial infarction.EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology · 2021
    Trial
  3. Trial
  4. Article
  5. Mass balance and metabolite profiling ofXenobiotica; the fate of foreign compounds in biological systems · 2026
    Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Jihong LiFrom the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and Pathology, Columbia University Medical Center, New York, NY (T.G.D.).
Spandana VootukuriFrom the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and Pathology, Columbia University Medical Center, New York, NY (T.G.D.).
Yi ShangFrom the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and Pathology, Columbia University Medical Center, New York, NY (T.G.D.).
Ana NegriFrom the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and Pathology, Columbia University Medical Center, New York, NY (T.G.D.).
Jian-Kang JiangFrom the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and Pathology, Columbia University Medical Center, New York, NY (T.G.D.).
Mark NedelmanFrom the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and Pathology, Columbia University Medical Center, New York, NY (T.G.D.).
Thomas G DiacovoFrom the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and Pathology, Columbia University Medical Center, New York, NY (T.G.D.).
Marta FilizolaFrom the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and Pathology, Columbia University Medical Center, New York, NY (T.G.D.).
Craig J ThomasFrom the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and Pathology, Columbia University Medical Center, New York, NY (T.G.D.).
Barry S CollerFrom the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and Pathology, Columbia University Medical Center, New York, NY (T.G.D.). collerb@rockefeller.edu.
Abcam (United States) · USNational Center for Advancing Translational Sciences · USNational Institutes of Health · USIcahn School of Medicine at Mount Sinai · US

Funding

NIH Chemical Genomics CenterZIBTR000004 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI MCKEW, JOHN · 2012 to 2014
$52.3M
Transforming Translational Science and Education to Benefit Human HealthUL1TR000043 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY · 2012 to 2015
$26.8M
Platelet Integrin AlphaIIbBeta3 Structure, Activation, and Ligand Binding: Fibrinogen, Fibrin, D-dimer, and von Willebrand FactorR01HL019278 · NHLBI · STATE UNIVERSITY NEW YORK STONY BROOK · PI Claudia Lorena Buitrago, Barry Coller · 1985 to 2026
$17.6M
Training and Mentoring ProgramsU54CA143930 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PIETRAS, RICHARD JOSEPH · 2009 to 2020
$7.5M
NCATS NIH HHS UL1 TR000043NCATS NIH HHS UL1TR000043NCI NIH HHS U54CA143930NHLBI NIH HHS R01 HL019278
6 · The paper itself

Abstract

objectiveTreatment of myocardial infarction within the first 1 to 2 hours with a thrombolytic agent, percutaneous coronary intervention, or an αIIbβ3 antagonist decreases mortality and the later development of heart failure. We previously reported on a novel small molecule αIIbβ3 antagonist, RUC-2, that has a unique mechanism of action. We have now developed a more potent and more soluble congener of RUC-2, RUC-4, designed to be easily administered intramuscularly by autoinjector to facilitate its use in the prehospital setting. Here, we report the properties of RUC-4 and the antiplatelet and antithrombotic effects of RUC-2 and RUC-4 in animal models. APPROACH AND

resultsRUC-4 was ≈ 20% more potent than RUC-2 in inhibiting human ADP-induced platelet aggregation and much more soluble in aqueous solutions (60-80 mg/mL). It shared RUC-2's specificity for αIIbβ3 versus αVβ3, did not prime the receptor to bind fibrinogen, or induce changes in β3 identified by a conformation-specific monoclonal antibody. Both RUC-2 and RUC-4 prevented FeCl3-induced thrombotic occlusion of the carotid artery in mice and decreased microvascular thrombi in response to laser injury produced by human platelets infused into transgenic mice containing a mutated von Willebrand factor that reacts with human but not mouse platelets. Intramuscular injection of RUC-4 in nonhuman primates at 1.9 and 3.85 mg/kg led to complete inhibition of platelet aggregation within 15 minutes, with dose-dependent return of platelet aggregation after 4.5 to 24 hours.

conclusionsRUC-4 has favorable biochemical, pharmacokinetic, pharmacodynamic, antithrombotic, and solubility properties as a prehospital therapy of myocardial infarction, but the possibility of increased bleeding with therapeutic doses remains to be evaluated.

Indexed as

Emergency Medical ServicesAnimalsBinding SitesBlood PlateletsCarotid StenosisChloridesDisease Models, AnimalFerric CompoundsFibrinolytic AgentsHumansMacaca fascicularisMaleMiceMice, TransgenicMolecular Dynamics SimulationMyocardial InfarctionChloridesferric chlorideFerric CompoundsFibrinolytic AgentsPlatelet Aggregation InhibitorsPlatelet Glycoprotein GPIIb-IIIa ComplexPyrimidinonesRUC-4 compoundThiadiazolesvon Willebrand Factorblood plateletsmyocardial infarction

Identifiers

PMID25147334
PMCPMC4180209
OpenAlexW2113192711

What OpenQuestion 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 OpenQuestion graph.