ArticleJournal of thrombosis and haemostasis : JTH2021
A novel vitamin K derived anticoagulant tolerant to genetic variations of vitamin K epoxide reductase.
Article in Journal of thrombosis and haemostasis : JTH, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Small-molecule inhibition of γ-glutamyl carboxylase reveals a novel anticoagulant strategy.Blood advances · 2026Article
- Warfarin-GPRP: Development and Evaluation of a Novel Warfarin-Based Peptide Conjugate for Enhanced Anticoagulant Activity.ACS omega · 2026Article
- An Overview of Anticoagulant Drugs Pharmacology, Therapeutic Approaches, Limitations and Perspectives.Pharmaceutics · 2026Review
- Causal Effects of Atrial Fibrillation and Warfarin Use on Osteoporosis Risk: A Two-Sample Mendelian Randomization Analysis.International journal of genomics · 2026Article
- Review
- VKORC1 polymorphisms and complete resistance to vitamin K antagonists: About two cases.BioMedicine · 2024Article
- Article
- Drug-microbiota interactions: an emerging priority for precision medicine.Signal transduction and targeted therapy · 2023Review
- Synthesis of new vitamin K derivatives with a ketone group at the C-1' position of the side chain and their conversion to menaquinone-4.Journal of molecular structure · 2023Article
- Naturally occurring UBIAD1 mutations differentially affect menaquinone biosynthesis and vitamin K-dependent carboxylation.The FEBS journal · 2022Article
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundVitamin K antagonists (VKAs), such as warfarin, have remained the cornerstone of oral anticoagulation therapy in the prevention and treatment of thromboembolism for more than half a century. They function by impairing the biosynthesis of vitamin K-dependent (VKD) clotting factors through the inhibition of vitamin K epoxide reductase (VKOR). The challenge of VKAs therapy is their narrow therapeutic index and highly variable dosing requirements, which are partially the result of genetic variations of VKOR.
objectivesThe goal of this study was to search for an improved VKA that is tolerant to the genetic variations of its target enzyme.
methodsA series of vitamin K derivatives with benzyl and related side-chain substitutions at the 3-position of 1,4-naphthoquinone were synthesized. The role of these compounds in VKD carboxylation was evaluated by mammalian cell-based assays and conventional in vitro activity assays.
resultsOur results showed that replacing the phytyl side-chain with a methylene cyclooctatetraene (COT) moiety at the 3-position of vitamin K
conclusionWe discovered a vitamin K analogue that functions as a VKA and is tolerant to genetic variations in the target enzyme.
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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.