ArticleJournal of thrombosis and haemostasis : JTH2016
Allosterism-based simultaneous, dual anticoagulant and antiplatelet action: allosteric inhibitor targeting the glycoprotein Ibα-binding and heparin-binding site of thrombin.
Article in Journal of thrombosis and haemostasis : JTH, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Lignins and Their Derivatives with Beneficial Effects on Human Health.International journal of molecular sciences · 2017Pooled it
- pH-Responsive Amphiphilic Chitosan-Lignin System Loaded with Samarium Oxide Nanoparticles for Curcumin Delivery.ACS omega · 2025Article
- A Robust Proteomics-Based Method for Identifying Preferred Protein Targets of Synthetic Glycosaminoglycan Mimetics.bioRxiv : the preprint server for biology · 2025Article
- Merging cultures and disciplines to create a drug discovery ecosystem at Virginia commonwealth university: Medicinal chemistry, structural biology, molecular and behavioral pharmacology and computational chemistry.SLAS discovery : advancing life sciences R & D · 2023Review
- Designing Smaller, Synthetic, Functional Mimetics of Sulfated Glycosaminoglycans as Allosteric Modulators of Coagulation Factors.Journal of medicinal chemistry · 2023Review
- Designing Synthetic, Sulfated Glycosaminoglycan Mimetics That Are Orally Bioavailable and ExhibitingJournal of medicinal chemistry · 2023Article
- An Efficient Method of Birch Ethanol Lignin Sulfation with a Sulfaic Acid-Urea Mixture.Molecules (Basel, Switzerland) · 2022Article
- Murine Models in the Evaluation of Heparan Sulfate-Based Anticoagulants.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Studies on fragment-based design of allosteric inhibitors of human factor XIa.Bioorganic & medicinal chemistry · 2020Article
- Intravital Assessment of Blood Platelet Function. A Review of the Methodological Approaches with Examples of Studies of Selected Aspects of Blood Platelet Function.International journal of molecular sciences · 2020Review
- Inhibition of Human Cytomegalovirus Entry into Host Cells Through a Pleiotropic Small Molecule.International journal of molecular sciences · 2020Article
- Sulfated Non-Saccharide Glycosaminoglycan Mimetics as Novel Drug Discovery Platform for Various Pathologies.Current medicinal chemistry · 2020Review
- A synthetic heparin mimetic that allosterically inhibits factor XIa and reduces thrombosis in vivo without enhanced risk of bleeding.Journal of thrombosis and haemostasis : JTH · 2019Article
- Thrombin Exosite Maturation and Ligand Binding at ABE II Help Stabilize PAR-Binding Competent Conformation at ABE I.Biochemistry · 2019Article
- A Unique Nonsaccharide Mimetic of Heparin Hexasaccharide Inhibits Colon Cancer Stem Cells via p38 MAP Kinase Activation.Molecular cancer therapeutics · 2019Article
- Lignin-Derived Biomaterials for Drug Release and Tissue Engineering.Molecules (Basel, Switzerland) · 2018Review
- Deciphering Conformational Changes Associated with the Maturation of Thrombin Anion Binding Exosite I.Biochemistry · 2017Article
- Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundAllosteric inhibition is a promising approach for developing a new group of anticoagulants with potentially reduced bleeding consequences. Recently, we designed sulfated β-O4 lignin (SbO4L) as an allosteric inhibitor that targets exosite 2 of thrombin to reduce fibrinogen cleavage through allostery and compete with glycoprotein Ibα to reduce platelet activation.
objectiveTo assess: (i) the antithrombotic potential of a novel approach of simultaneous exosite 2-dependent allosteric inhibition of thrombin and competitive inhibition of platelet activation; and (ii) the promise of SbO4L as the first-in-class antithrombotic agent.
methodsA combination of whole blood thromboelastography, hemostasis analysis, mouse arterial thrombosis models and mouse tail bleeding studies were used to assess antithrombotic potential. RESULTS AND
conclusionsSbO4L extended the clot initiation time, and reduced maximal clot strength, platelet contractile force, and the clot elastic modulus, suggesting dual anticoagulant and antiplatelet effects. These effects were comparable to those observed with enoxaparin. A dose of 1 mg of SbO4L per mouse prevented occlusion in 100% of arteries, and lower doses resulted in a proportionally reduced response. Likewise, the time to occlusion increased by ~ 70% with a 0.5-mg dose in the mouse Rose Bengal thrombosis model. Finally, tail bleeding studies demonstrated that SbO4L does not increase bleeding propensity. In comparison, a 0.3-mg dose of enoxaparin increased the bleeding time and blood volume loss. Overall, this study highlights the promise of the allosteric inhibition approach, and presents SbO4L as a novel anticoagulant with potentially reduced bleeding side effects.
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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.