ArticleJournal of medicinal chemistry2011
Designing nonsaccharide, allosteric activators of antithrombin for accelerated inhibition of factor Xa.
Article in Journal of medicinal chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 34 citations in OpenAlex.
- Fully Synthetic Non-Carbohydrate Heparin Mimetics-Perspectives for Therapeutic Anticoagulation and Beyond?Archiv der Pharmazie · 2026Review
- Glycosaminoglycans as Polyelectrolytes: Charge, Interactions, and Applications.Chembiochem : a European journal of chemical biology · 2025Review
- Discovery of Heparin Mimetic, Potent, and Selective Inhibitors of Human Clotting Factor XIIIa.ACS omega · 2024Article
- Designing Smaller, Synthetic, Functional Mimetics of Sulfated Glycosaminoglycans as Allosteric Modulators of Coagulation Factors.Journal of medicinal chemistry · 2023Review
- Designing Synthetic, Sulfated Glycosaminoglycan Mimetics That Are Orally Bioavailable and ExhibitingJournal of medicinal chemistry · 2023Article
- Factor XIIIa inhibitors as potential novel drugs for venous thromboembolism.European journal of medicinal chemistry · 2020Review
- Article
- The Pictet-Spengler Reaction Updates Its Habits.Molecules (Basel, Switzerland) · 2020Review
- Sulfated Non-Saccharide Glycosaminoglycan Mimetics as Novel Drug Discovery Platform for Various Pathologies.Current medicinal chemistry · 2020Review
- Inhibition of Herpes Simplex Virus-1 Entry into Human Cells by Nonsaccharide Glycosaminoglycan Mimetics.ACS medicinal chemistry letters · 2018Article
- Cooperative Interactions of Three Hotspot Heparin Binding Residues Are Critical for Allosteric Activation of Antithrombin by Heparin.Biochemistry · 2018Article
- Sulfotransferase and Heparanase: Remodeling Engines in Promoting Virus Infection and Disease Development.Frontiers in pharmacology · 2018Review
- Potent, Selective, Allosteric Inhibition of Human Plasmin by Sulfated Non-Saccharide Glycosaminoglycan Mimetics.Journal of medicinal chemistry · 2017Article
- Article
- Plasmin regulation through allosteric, sulfated, small molecules.Molecules (Basel, Switzerland) · 2015Article
- Recent advances on plasmin inhibitors for the treatment of fibrinolysis-related disorders.Medicinal research reviews · 2014Review
- Synthetic, non-saccharide, glycosaminoglycan mimetics selectively target colon cancer stem cells.ACS chemical biology · 2014Article
- Designing allosteric inhibitors of factor XIa. Lessons from the interactions of sulfated pentagalloylglucopyranosides.Journal of medicinal chemistry · 2014Article
- Allosteric inhibition of human factor XIa: discovery of monosulfated benzofurans as a class of promising inhibitors.Journal of medicinal chemistry · 2014Article
- Discovery of allosteric modulators of factor XIa by targeting hydrophobic domains adjacent to its heparin-binding site.Journal of medicinal chemistry · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Antithrombin is a key regulator of coagulation and prime target of heparins, clinically used anticoagulants. Heparins induce a two-step conformational activation of antithrombin, a process that has remained challenging to target with molecules devoid of the antithrombin-binding pentasaccharide DEFGH. Computational screening of a focused library led to the design of two tetra-sulfated N-arylacyl tetrahydroisoquinoline variants as potential nonsaccharide activators of antithrombin. A high yielding synthetic scheme based on Horner-Wadsworth-Emmons or Pictet-Spengler reactions was developed to facilitate the functionalization of the tetrahydoisoquinoline ring, which upon further amidation, deprotection, and sulfation gave the targeted nonsaccharide activators. Spectrofluorometric measurement of affinity displayed antithrombin binding affinities in the low to high micromolar range at pH 6.0, I 0.05, 25 °C. Measurement of second-order rate constants of antithrombin inhibition of factor Xa in the presence and absence of the designed activators showed antithrombin activation in the range of 8-80-fold in the pH 6.0 buffer. This work puts forward 20c, a novel tetra-sulfated N-arylacyl tetrahydroisoquinoline-based molecule, that activates AT only 3.8-fold less than that achieved with DEFGH, suggesting a strong possibility of rationally designing sulfated organic molecules as clinically relevant AT activators.
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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.