ArticleJournal of medicinal chemistry2014
Allosteric inhibition of human factor XIa: discovery of monosulfated benzofurans as a class of promising inhibitors.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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
15 citing papers in PubMed, 27 citations in OpenAlex.
- First randomized evaluation of safety, pharmacodynamics, and pharmacokinetics of BAY 1831865, an antibody targeting coagulation factor XI and factor XIa, in healthy men.Journal of thrombosis and haemostasis : JTH · 2022Trial
- Translational Development of Oral FXIa Inhibitors: A Systematic Review of Molecular Design, Pharmacology, and Indication-Specific Clinical Evidence.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The Discovery of a Novel Anticoagulant Mechanism: Factor XI Activation Inhibitors.ACS pharmacology & translational science · 2025Article
- Development of an Ultrasensitive Competitive Double-Enzyme Cascade Fluorescence Signal Amplification Method for Factor XIa Inhibitor Screening.Analytical chemistry · 2024Article
- 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
- Studies on fragment-based design of allosteric inhibitors of human factor XIa.Bioorganic & medicinal chemistry · 2020Article
- 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
- On the Process of Discovering Leads That Target the Heparin-Binding Site of Neutrophil Elastase in the Sputum of Cystic Fibrosis Patients.Journal of medicinal chemistry · 2019Article
- Recent advances in the discovery and development of factor XI/XIa inhibitors.Medicinal research reviews · 2018Review
- Selection and characterization of a DNA aptamer inhibiting coagulation factor XIa.Scientific reports · 2017Article
- Potent, Selective, Allosteric Inhibition of Human Plasmin by Sulfated Non-Saccharide Glycosaminoglycan Mimetics.Journal of medicinal chemistry · 2017Article
- Article
- Designing allosteric inhibitors of factor XIa. Lessons from the interactions of sulfated pentagalloylglucopyranosides.Journal of medicinal chemistry · 2014Article
- Thiocarbamate-linked polysulfonate-peptide conjugates as selective hepatocyte growth factor receptor binders.Bioconjugate chemistry · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Factor XIa (fXIa) is being recognized as a prime target for developing safer anticoagulants. To discover synthetic, small, allosteric inhibitors of fXIa, we screened an in-house, unique library of 65 molecules displaying many distinct scaffolds and varying levels of sulfation. Of these, monosulfated benzofurans were the only group of molecules found to inhibit fXIa (∼100% efficacy) and led to the identification of monosulfated trimer 24 (IC50 0.82 μM) as the most potent inhibitor. Michaelis-Menten kinetics studies revealed a classic noncompetitive mechanism of action for 24. Although monosulfated, the inhibitors did not compete with unfractionated heparin alluding to a novel site of interaction. Fluorescence quenching studies indicated that trimer 24 induces major conformational changes in the active site of fXIa. Docking studies identified a site near Lys255 on the A3 domain of fXIa as the most probable site of binding for 24. Factor XIa devoid of the A3 domain displayed a major defect in the inhibition potency of 24 supporting the docking prediction. Our work presents the sulfated benzofuran scaffold as a promising framework to develop allosteric fXIa inhibitors that likely function through the A3 domain.
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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.