ArticleJournal of medicinal chemistry2013
Discovery of allosteric modulators of factor XIa by targeting hydrophobic domains adjacent to its heparin-binding site.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Investigation of the anticoagulant activity of cyclic sulfated glycosaminoglycan mimetics.Carbohydrate research · 2023Article
- Designing Smaller, Synthetic, Functional Mimetics of Sulfated Glycosaminoglycans as Allosteric Modulators of Coagulation Factors.Journal of medicinal chemistry · 2023Review
- Factor XI, a potential target for anticoagulation therapy for venous thromboembolism.Frontiers in cardiovascular medicine · 2022Review
- Studies on fragment-based design of allosteric inhibitors of human factor XIa.Bioorganic & medicinal chemistry · 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
- Recent advances in the discovery and development of factor XI/XIa inhibitors.Medicinal research reviews · 2018Review
- Inhibition of Herpes Simplex Virus-1 Entry into Human Cells by Nonsaccharide Glycosaminoglycan Mimetics.ACS medicinal chemistry letters · 2018Article
- Potent, Selective, Allosteric Inhibition of Human Plasmin by Sulfated Non-Saccharide Glycosaminoglycan Mimetics.Journal of medicinal chemistry · 2017Article
- Article
- The hemostatic role of factor XI.Thrombosis research · 2016Review
- Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin.Scientific reports · 2016Article
- Factor XIa inhibitors: A review of the patent literature.Expert opinion on therapeutic patents · 2016Review
- Allosteric inhibition of factor XIa. Sulfated non-saccharide glycosaminoglycan mimetics as promising anticoagulants.Thrombosis research · 2015Article
- Plasmin regulation through allosteric, sulfated, small molecules.Molecules (Basel, Switzerland) · 2015Article
- Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry.Beilstein journal of organic chemistry · 2015Review
- Future prospects for contact factors as therapeutic targets.Hematology. American Society of Hematology. Education Program · 2014Review
- Recent advances on plasmin inhibitors for the treatment of fibrinolysis-related disorders.Medicinal research reviews · 2014Review
- Factor XI as a target for antithrombotic therapy.Drug discovery today · 2014Review
- Synthetic, non-saccharide, glycosaminoglycan mimetics selectively target colon cancer stem cells.ACS chemical biology · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
To discover promising sulfated allosteric modulators (SAMs) of glycosaminoglycan-binding proteins (GBPs), such as human factor XIa (FXIa), we screened a library of 26 synthetic, sulfated quinazolin-4(3H)-ones (QAOs) resulting in the identification of six molecules that reduced the Vmax of substrate hydrolysis without influencing the KM. Mutagenesis of residues of the heparin-binding site (HBS) of FXIa introduced a nearly 5-fold loss in inhibition potency supporting recognition of an allosteric site. Fluorescence studies showed a sigmoidal binding profile indicating highly cooperative binding. Competition with a positively charged, heparin-binding polymer did not fully nullify inhibition suggesting importance of hydrophobic forces to binding. This discovery suggests the operation of a dual-element recognition process, which relies on an initial Coulombic attraction of anionic SAMs to the cationic HBS of FXIa that forms a locked complex through tight interaction with an adjacent hydrophobic patch. The dual-element strategy may be widely applicable for discovering SAMs of other GBPs.
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What OpenQuestion holds
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.