ArticleCirculation2012
Suppression of arterial thrombosis without affecting hemostatic parameters with a cell-penetrating PAR1 pepducin.
Article in Circulation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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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.
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.
Who cites it
40 citing papers in PubMed, 86 citations in OpenAlex.
- PAR1 (Protease-Activated Receptor 1) Pepducin Therapy Targeting Myocardial Necrosis in Coronary Artery Disease and Acute Coronary Syndrome Patients Undergoing Cardiac Catheterization: A Randomized, Placebo-Controlled, Phase 2 Study.Arteriosclerosis, thrombosis, and vascular biology · 2020Trial
- A neurotensin receptor type 1-derived pepducin acts as a biased allosteric modulator to regulate target receptor function.Acta pharmaceutica Sinica. B · 2026Article
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- Protease-activated receptor 1 in diabetes and its chronic complications: signaling mechanisms and emerging therapeutic advances.Frontiers in pharmacology · 2026Review
- Exploring the Chemical Features and Biomedical Relevance of Cell-Penetrating Peptides.International journal of molecular sciences · 2024Review
- Cancer-Targeting Applications of Cell-Penetrating Peptides.International journal of molecular sciences · 2024Review
- Suppression of Heart Failure With PAR1 Pepducin Technology in a Pressure Overload Model in Mice.Circulation. Heart failure · 2023Article
- Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands.International journal of molecular sciences · 2023Review
- Lipopeptide Pepducins as Therapeutic Agents.Methods in molecular biology (Clifton, N.J.) · 2022Article
- A KLK4 proteinase substrate capture approach to antagonize PAR1.Scientific reports · 2021Article
- Deficiency of MMP1a (Matrix Metalloprotease 1a) Collagenase Suppresses Development of Atherosclerosis in Mice: Translational Implications for Human Coronary Artery Disease.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Allosteric Modulator Leads Hiding in Plain Site: Developing Peptide and Peptidomimetics as GPCR Allosteric Modulators.Frontiers in chemistry · 2021Review
- Platelet-Cancer Interplay: Molecular Mechanisms and New Therapeutic Avenues.Frontiers in oncology · 2021Review
- Lipid Receptor GPR31 (G-Protein-Coupled Receptor 31) Regulates Platelet Reactivity and Thrombosis Without Affecting Hemostasis.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Targeting of G-protein coupled receptors in sepsis.Pharmacology & therapeutics · 2020Review
- pHLIP(Var7)-P1AP suppresses tumor cell proliferation in MDA-MB-231 triple-negative breast cancer by targeting protease activated receptor 1.Breast cancer research and treatment · 2020Article
- PAR2 Pepducin-Based Suppression of Inflammation and Itch in Atopic Dermatitis Models.The Journal of investigative dermatology · 2019Article
- Protease-Activated Receptor 1 as Therapeutic Target in Breast, Lung, and Ovarian Cancer: Pepducin Approach.International journal of molecular sciences · 2018Review
- Novel aspects of antiplatelet therapy in cardiovascular disease.Research and practice in thrombosis and haemostasis · 2018Review
- Noncanonical Matrix Metalloprotease 1-Protease-Activated Receptor 1 Signaling Drives Progression of Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThrombin-dependent platelet activation is heightened in the setting of percutaneous coronary intervention and may cause arterial thrombosis with consequent myocardial necrosis. Given the high incidence of adverse effects in patients with acute coronary syndromes, there remains an unmet need for the development of new therapeutics that target platelet activation without unduly affecting hemostasis. The thrombin receptor, PAR1, has recently emerged as a promising new target for therapeutic intervention in patients with acute coronary syndromes. METHODS AND
resultsWe report the development of a first-in-class intracellular PAR1 inhibitor with optimized pharmacokinetic properties for use during percutaneous coronary intervention in patients with acute coronary syndromes. PZ-128 is a cell-penetrating pepducin inhibitor of PAR1 that targets the receptor-G-protein interface on the inside surface of platelets. The structure of PZ-128 closely resembles the predicted off-state of the corresponding juxtamembrane region of the third intracellular loop of PAR1. The onset of action of PZ-128 was rapid and suppressed PAR1 aggregation and arterial thrombosis in guinea pigs and baboons and strongly synergized with oral clopidogrel. There was full recovery of platelet function by 24 hours. Importantly, PZ-128 had no effect on bleeding or coagulation parameters in primates or in blood from patients undergoing percutaneous coronary intervention.
conclusionsBased on the efficacy data in nonhuman primates with no noted adverse effects on hemostasis, we anticipate that the rapid onset of platelet inhibition and reversible properties of PZ-128 are well suited to the acute interventional setting of percutaneous coronary intervention and may provide an alternative to long-acting small-molecule inhibitors of PAR1.
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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.