ReviewBlood2023
Targeting biased signaling by PAR1: function and molecular mechanism of parmodulins.
Review in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
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Who cites it
28 citing papers in PubMed, 27 citations in OpenAlex.
- Activated protein C promotes hematopoietic stem and progenitor cell quiescence and engraftment.EMBO molecular medicine · 2026Article
- G protein-coupled receptor-mediated platelet thrombus formation.Current opinion in hematology · 2026Review
- Epithelial PCSK6 Promotes Proliferation and Decreases Collagen Deposition by Fibroblasts Potentially via MMP Activation.International journal of molecular sciences · 2026Article
- Thrombin is increased in diabetic retinal pathology in the STZ mice model, and its attenuation by a specific inhibitor, PARIN5, is associated with preserved function.Scientific reports · 2026Article
- Understanding how a highly prevalent GRK5 polymorphism affects platelets and enhances thrombotic risk.Blood · 2026Article
- Targeting PAR1 biased signaling with parmodulin reduces thromboinflammation and acute lung injury in sickle cell disease.Blood advances · 2026Article
- Signaling bias of the protease-activated receptor-1 is dictated by distinct GRK5 and β-arrestin-2 determinants.Cell reports · 2026Article
- Computational analysis of the structural and functional impact of the deleterious nsSNPs in the humanBiochemistry and biophysics reports · 2026Article
- Activated Protein C and the Retina: From Physiology to Therapeutic Potential.International journal of molecular sciences · 2026Review
- Protease-activated receptor 1 in diabetes and its chronic complications: signaling mechanisms and emerging therapeutic advances.Frontiers in pharmacology · 2026Review
- Gut-primed neutrophils activate Kupffer cells to promote hepatic injury in mouse sepsis.Nature communications · 2025Article
- Activated protein C ameliorates diabetes-induced atherosclerosis by sustaining macrophage efferocytosis.Cardiovascular diabetology · 2025Article
- Endothelial NMMHC IIA dissociation from PAR1 activates the CREB3/ARF4 signaling in thrombin-mediated intracerebral hemorrhage.Journal of advanced research · 2025Article
- Novel Function for Endothelial Protease-Activated Receptors in Modulating Insulin Receptor Activity With Implications for Diabetes.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- A Bivalent Protease-Activated Receptor-Derived Peptide Mimics Neuronal Anti-Apoptotic Activity of Activated Protein C.Bioengineering (Basel, Switzerland) · 2025Article
- From theory to platelets: unraveling the history and complexities of biased signaling.Blood vessels, thrombosis & hemostasis · 2025Review
- Collecting lymphatics unzip to drain injured lungs.Nature cardiovascular research · 2025Article
- The thrombin receptor PAR1 orchestrates changes in lymphatic endothelial cell junction morphology to augment lymphatic drainage during lung injury.Nature cardiovascular research · 2025Article
- Systemic Impact of Platelet Activation in Abdominal Surgery: From Oxidative and Inflammatory Pathways to Postoperative Complications.International journal of molecular sciences · 2025Review
- PAR-1 Expression in Chronic Subdural Hematoma: Potential Association with Vascular Permeability.Neurotrauma reports · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The G protein-coupled receptor (GPCR) protease-activated receptor 1 (PAR1) is a therapeutic target that was originally pursued with the aim of restricting platelet activation and the burden of cardiovascular diseases. In clinical studies, the use of orthosteric PAR1 inhibitors was associated with an increased risk of hemorrhage, including intracranial hemorrhage. Because (1) PAR1 is expressed by various cell types, including endothelial cells, (2) conveys in mice a physiological indispensable function for vascular development during embryogenesis, and (3) is subject to biased signaling dependent on the activating proteases, orthosteric PAR1 inhibition may be associated with unwanted side effects. Alternatively, the protease-activated protein C (aPC) and its variants can promote valuable anti-inflammatory signaling via PAR1. Most recently, small molecule allosteric modulators of PAR1 signaling, called parmodulins, have been developed. Parmodulins inhibit coagulation and platelet activation yet maintain cytoprotective effects typically provoked by PAR1 signaling upon the activation by aPC. In this study, we review the discovery of parmodulins and their preclinical data, summarize the current knowledge about their mode of action, and compare the structural interaction of parmodulin and PAR1 with that of other intracellularly binding allosteric GPCR modulators. Thus, we highlight the pharmaceutical potential and challenges associated with the future development of parmodulins.
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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.