ReviewCurrent medicinal chemistry2010
Regulation of the protein C anticoagulant and antiinflammatory pathways.
Review in Current medicinal chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- Endotheliopathy in Acute COVID-19 and Long COVID.International journal of molecular sciences · 2023Pooled it
- Article
- Management of Severe Congenital Protein C Deficiency with Continuous Subcutaneous Infusion via Insulin Pump: A Pediatric Case Report.Children (Basel, Switzerland) · 2026Article
- Activated Protein C and the Retina: From Physiology to Therapeutic Potential.International journal of molecular sciences · 2026Review
- Mediating role of proteomics in the association between per- and polyfluoroalkyl substance exposure and blood pressure in youth.Environmental pollution (Barking, Essex : 1987) · 2025Article
- Bioinformatic analysis of rare endothelial protein C receptor missense variants associated with coagulation and thrombophilia risk.Scientific reports · 2025Article
- Diagnostic Value of Protein C Depletion in Pathologies Associated with the Activation of the Blood Coagulation System.International journal of molecular sciences · 2025Article
- Evaluation of pharmacokinetics of intravenous protein C concentrate in protein C deficiency: implications for treatment initiation and maintenance.Research and practice in thrombosis and haemostasis · 2025Article
- The Multifaceted Roles of Thrombomodulin: Anti-coagulation, Anti-inflammation, and Anti-tumor Potential.Current pharmaceutical design · 2025Review
- Exploring the Diversity and Function of Serine Proteases in Toxicofera Reptile Venoms: A Comprehensive Overview.Toxins · 2024Review
- Comprehensive literature review of protein C concentrate use in patients with severe congenital protein C deficiency.Research and practice in thrombosis and haemostasis · 2024Review
- Biased agonism of protease-activated receptor-1 regulates thromboinflammation in murine sickle cell disease.Blood advances · 2024Article
- Unraveling the Molecular Mechanisms of Activated Protein C (APC) in Mitigating Reperfusion Injury and Cardiac Ischemia: a Promising Avenue for Novel Therapeutic Interventions.Journal of cardiovascular translational research · 2024Review
- Review
- Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus.Nature communications · 2022Article
- Integral and Local Methods for the Evaluation of the Hemostasiological Profile in Sheep at Various Stages of Implantation of a Biodegradable Vascular Graft.Sovremennye tekhnologii v meditsine · 2022Article
- Exosite Binding in Thrombin: A Global Structural/Dynamic Overview of Complexes with Aptamers and Other Ligands.International journal of molecular sciences · 2021Review
- PAR1 regulation of CXCL1 expression and neutrophil recruitment to the lung in mice infected with influenza A virus.Journal of thrombosis and haemostasis : JTH · 2021Article
- Role of emerging vitamin K‑dependent proteins: Growth arrest‑specific protein 6, Gla‑rich protein and periostin (Review).International journal of molecular medicine · 2021Review
- Protein C Pathway in Paediatric and Neonatal Sepsis.Frontiers in pediatrics · 2021Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Protein C is a vitamin K-dependent anticoagulant serine protease zymogen in plasma which upon activation by the thrombin-thrombomodulin complex down-regulates the coagulation cascade by degrading cofactors Va and VIIIa by limited proteolysis. In addition to its anticoagulant function, activated protein C (APC) also binds to endothelial protein C receptor (EPCR) in lipid-rafts/caveolar compartments to activate protease- activated receptor 1 (PAR-1) thereby eliciting antiinflammatory and cytoprotective signaling responses in endothelial cells. These properties have led to FDA approval of recombinant APC as a therapeutic drug for severe sepsis. The mechanism by which APC selects its substrates in the anticoagulant and antiinflammatory pathways is not well understood. Recent structural and mutagenesis data have indicated that basic residues of three exposed surface loops known as 39-loop (Lys-37, Lys-38, and Lys-39), 60-loop (Lys-62, Lys- 63, and Arg-67), and 70-80-loop (Arg-74, Arg-75, and Lys-78) (chymotrypsin numbering) constitute an anion binding exosite in APC that interacts with the procoagulant cofactors Va and VIIIa in the anticoagulant pathway. Furthermore, two negatively charged residues on the opposite side of the active-site of APC on a helical structure have been demonstrated to determine the specificity of the PAR-1 recognition in the cytoprotective pathway. This article will review the mechanism by which APC exerts its proteolytic function in two physiologically inter-related pathways and how the structure- function insights into determinants of the specificity of APC interaction with its substrates in two pathways can be utilized to tinker with the structure of the molecule to obtain APC derivatives with potentially improved therapeutic profiles.
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What OpenQuestion holds
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.