ArticleJournal of thrombosis and haemostasis : JTH2020
Novel inhibitor ZED3197 as potential drug candidate in anticoagulation targeting coagulation FXIIIa (F13a).
Article in Journal of thrombosis and haemostasis : JTH, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Increased number of crosslinking sites for factor XIII counteracts the mechanical and lytic destabilization of fibrin caused by citrullination of fibrinogen.Frontiers in immunology · 2026Article
- Determination of Patient-Specific Blood Coagulation Kinetic Parameters via Neural Networks: Toward Thrombosis Prediction in Personalized Medicine.Annals of biomedical engineering · 2025Article
- The third-generation anticoagulants: factors XI, XII, and XIII inhibitors.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2024Review
- Discovery of Heparin Mimetic, Potent, and Selective Inhibitors of Human Clotting Factor XIIIa.ACS omega · 2024Article
- Progress of nanomaterials in the treatment of thrombus.Drug delivery and translational research · 2024Review
- The role of coagulome in the tumor immune microenvironment.Advanced drug delivery reviews · 2023Review
- Fbg αC 389-402 Enhances Factor XIII Cross-Linking in the Fibrinogen αC Region Via Electrostatic and Hydrophobic Interactions.Biochemistry · 2023Article
- Peptidic Inhibitors and a Fluorescent Probe for the Selective Inhibition and Labelling of Factor XIIIa Transglutaminase.Molecules (Basel, Switzerland) · 2023Article
- Fibrinogen and Factor XIII in Venous Thrombosis and Thrombus Stability.Arteriosclerosis, thrombosis, and vascular biology · 2022Review
- Ethacrynic acid is an inhibitor of human factor XIIIa.BMC pharmacology & toxicology · 2022Article
- Article
- State-of-the-art review - A review on snake venom-derived antithrombotics: Potential therapeutics for COVID-19-associated thrombosis?International journal of biological macromolecules · 2021Review
- Recombinant Destabilase fromCurrent issues in molecular biology · 2021Article
- Extracellular Histones Inhibit Fibrinolysis through Noncovalent and Covalent Interactions with Fibrin.Thrombosis and haemostasis · 2021Article
- Factor XIII-A: An Indispensable "Factor" in Haemostasis and Wound Healing.International journal of molecular sciences · 2021Review
- Factor XIII and Fibrin Clot Properties in Acute Venous Thromboembolism.International journal of molecular sciences · 2021Review
- NMR-Based Structural Characterization of a Two-Disulfide-Bonded Analogue of the FXIIIa Inhibitor Tridegin: New Insights into Structure-Activity Relationships.International journal of molecular sciences · 2021Article
- Article
- Factor XIIIa inhibitors as potential novel drugs for venous thromboembolism.European journal of medicinal chemistry · 2020Review
- Structure-Based Design of FXIIIa-Blockers: Addressing a Transient Hydrophobic Pocket in the Active Site of FXIIIa.ChemMedChem · 2020Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFactor XIII (FXIII) is the final enzyme of the coagulation cascade. While the other enzymatic coagulation factors are proteases, FXIII belongs to the transglutaminase family. FXIIIa covalently crosslinks the fibrin clot and represents a promising target for drug development to facilitate fibrinolysis. However, no FXIII-inhibiting compound has entered clinical trials. Here, we introduce the features of a peptidomimetic inhibitor of FXIIIa (ZED3197) as a potential drug candidate.
methodsThe potency of ZED3197 against FXIIIa and the selectivity against other human transglutaminases were characterized using transamidation and isopeptidase assays. The inhibition of fibrin crosslinking was evaluated by biochemical methods and thromboelastometry. Further, the pharmacology of the compound was explored in a rabbit model of venous stasis and reperfusion.
resultsZED3197 proved to be a potent and selective inhibitor of human FXIIIa. Further, the compound showed broad inhibitory activity against cellular FXIIIA from various animal species. Rotational thromboelastometry in whole human blood indicated that the inhibitor, in a dose-dependent manner, prolonged clot formation, reduced clot firmness, and facilitated clot lysis without affecting the clotting time, indicating minimal impact on hemostasis. In vivo, the novel FXIIIa inhibitor effectively decreased the weight of clots and facilitated flow restoration without prolongation of the bleeding time.
conclusionsZED3197 is the first drug-like potent compound targeting FXIIIa, a yet untapped target in anticoagulation. Due to the function of FXIII downstream of thrombin the approach provides minimal impact on hemostasis. In vivo data imply that the inhibitor dissociates an antithrombotic effect from increased bleeding tendency.
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