ArticleJournal of medicinal chemistry2013
Designing allosteric regulators of thrombin. Exosite 2 features multiple subsites that can be targeted by sulfated small molecules for inducing inhibition.
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 30 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
30 citing papers in PubMed, 51 citations in OpenAlex.
- Fully Synthetic Non-Carbohydrate Heparin Mimetics-Perspectives for Therapeutic Anticoagulation and Beyond?Archiv der Pharmazie · 2026Review
- Biomedical applications of engineered heparin-based materials.Bioactive materials · 2024Review
- 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
- Designing Synthetic, Sulfated Glycosaminoglycan Mimetics That Are Orally Bioavailable and ExhibitingJournal of medicinal chemistry · 2023Article
- 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
- 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
- Allosteric inhibition of α-thrombin enzymatic activity with ultrasmall gold nanoparticles.Nanoscale advances · 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
- Novel heparin mimetics reveal cooperativity between exosite 2 and sodium-binding site of thrombin.Thrombosis research · 2018Article
- A small group of sulfated benzofurans induces steady-state submaximal inhibition of thrombin.Bioorganic & medicinal chemistry letters · 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
- Discovery of an enzyme and substrate selective inhibitor of ADAM10 using an exosite-binding glycosylated substrate.Scientific reports · 2016Article
- Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin.Scientific reports · 2016Article
- Allosterism-based simultaneous, dual anticoagulant and antiplatelet action: allosteric inhibitor targeting the glycoprotein Ibα-binding and heparin-binding site of thrombin.Journal of thrombosis and haemostasis : JTH · 2016Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
We recently designed a group of novel exosite-2-directed sulfated, small, allosteric inhibitors of thrombin. To develop more potent inhibitors, monosulfated benzofuran tri- and tetrameric homologues of the parent designed dimers were synthesized in seven to eight steps and found to exhibit a wide range of potencies. Among these, trimer 9a was found to be nearly 10-fold more potent than the first generation molecules. Michaelis-Menten studies indicated an allosteric mechanism of inhibition. Competitive studies using a hirudin peptide (exosite 1 ligand) and unfractionated heparin, heparin octasaccharide, and γ'-fibrinogen peptide (exosite 2 ligands) demonstrated exosite 2 recognition in a manner different from that of the parent dimers. Alanine scanning mutagenesis of 12 Arg/Lys residues of exosite 2 revealed a defect in 9a potency for Arg233Ala thrombin only confirming the major difference in site of recognition between the two structurally related sulfated benzofurans. The results suggest that multiple avenues are available within exosite 2 for inducing thrombin inhibition.
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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.