ArticleNature communications2017
Engineered factor Xa variants retain procoagulant activity independent of direct factor Xa inhibitors.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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
16 citing papers in PubMed.
- Molecular mechanism of cleavage at R271 during prothrombin activation revealed by cryo-EM.Blood · 2026Article
- Small-Molecule Factor Xa Inhibitors: Translational SAR, Assay-Aware Data Quality, and QSAR-Readiness for CADD-Oriented Discovery.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Coagulation assays for assessing the bypassing of factor Xa direct oral anticoagulants using VMX-C001.Research and practice in thrombosis and haemostasis · 2026Article
- Direct Oral Anticoagulant Inhibitors: Mode of Action, Clinical Aspects.Handbook of experimental pharmacology · 2026Review
- Modifications of the Prothrombin Active Site S4 Subpocket Confer Resistance to Dabigatran.Thrombosis and haemostasis · 2026Article
- Possible Factor Xa Resistance in a Patient Who Failed Apixaban and Rivaroxaban.Clinical case reports · 2024Article
- Engineering and evaluation of FXa bypassing agents that restore hemostasis following Apixaban associated bleeding.Nature communications · 2024Article
- Novel Thiourea and Oxime Ether Isosteviol-Based Anticoagulants: MD Simulation and ADMET Prediction.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis.Thrombosis and haemostasis · 2023Article
- Novel strategies in antithrombotic therapy: targeting thrombosis while preserving hemostasis.Frontiers in cardiovascular medicine · 2023Review
- Unexpected Dynamic Binding May Rescue the Binding Affinity of Rivaroxaban in a Mutant of Coagulation Factor X.Frontiers in molecular biosciences · 2022Article
- Green by Design: Convergent Synthesis, Computational Analyses, and Activity Evaluation of New FXa Inhibitors Bearing Peptide Triazole Linking Units.Pharmaceutics · 2021Article
- ptFVa (Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Blood coagulation factor X: molecular biology, inherited disease, and engineered therapeutics.Journal of thrombosis and thrombolysis · 2021Review
- An Update on the Reversal of Non-Vitamin K Antagonist Oral Anticoagulants.Advances in hematology · 2020Review
- Deriving Force-Field Parameters from First Principles Using a Polarizable and Higher Order Dispersion Model.Journal of chemical theory and computation · 2019Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The absence of an adequate reversal strategy to prevent and stop potential life-threatening bleeding complications is a major drawback to the clinical use of the direct oral inhibitors of blood coagulation factor Xa. Here we show that specific modifications of the substrate-binding aromatic S4 subpocket within the factor Xa active site disrupt high-affinity engagement of the direct factor Xa inhibitors. These modifications either entail amino-acid substitution of S4 subsite residues Tyr99 and/or Phe174 (chymotrypsinogen numbering), or extension of the 99-loop that borders the S4 subsite. The latter modifications led to the engineering of a factor Xa variant that is able to support coagulation in human plasma spiked with (supra-)physiological concentrations of direct factor Xa inhibitors. As such, this factor Xa variant has the potential to be employed to bypass the direct factor Xa inhibitor-mediated anticoagulation in patients that require restoration of blood coagulation.A major drawback in the clinical use of the oral anticoagulants that directly inhibit factor Xa in order to prevent blood clot formation is the potential for life threatening bleeding events. Here the authors describe factor Xa variants that are refractory to inhibition by these anticoagulants and could serve as rescue agents in treated patients.
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