ArticleNature communications2020
Structure-guided design of pure orthosteric inhibitors of αIIbβ3 that prevent thrombosis but preserve hemostasis.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- In vitro assessment and phase I randomized clinical trial of anfibatide a snake venom derived anti-thrombotic agent targeting human platelet GPIbα.Scientific reports · 2021Trial
- PSG6: A mitochondrially-targeted gentisic acid derivative exerts antiplatelet action via mitochondrial complex I inhibition.Redox biology · 2026Article
- Structural basis for the differential recognition of integrin αvβ3 by rhodostomin and trimucrin.Communications biology · 2026Article
- Review
- A Novel KGD-Based αIIbβ3 Antagonist Prevents Arterial Thrombosis While Preserving Hemostasis and Avoiding Thrombocytopenia.International journal of molecular sciences · 2025Article
- Switching Roles─Exploring Concentration-Dependent Agonistic versus Antagonistic Behavior of Integrin Ligands.Journal of medicinal chemistry · 2025Article
- Platelet spreading and clot retraction are regulated by 2 distinct αThe Journal of pharmacology and experimental therapeutics · 2025Article
- The Integrin Receptors: From Discovery to Structure to Medicines.Immunological reviews · 2025Review
- Platelet integrin αIIbβ3 plays a key role in a venous thrombogenesis mouse model.Nature communications · 2024Article
- Structural insights into the molecular recognition of integrin αVβ3 by RGD-containing ligands: The role of the specificity-determining loop (SDL).bioRxiv : the preprint server for biology · 2024Article
- Packaging of supplemented urokinase into alpha granules of in vitro-grown megakaryocytes for targeted nascent clot lysis.Blood advances · 2024Article
- Deep Vein Thrombosis Is Facilitated by Endothelial-Derived Extracellular Vesicles via the PDI-GRP94-GPIIb/IIIa Pathway in Mice.Journal of clinical medicine · 2023Article
- Structure, signal transduction, activation, and inhibition of integrin αIIbβ3.Thrombosis journal · 2023Review
- Article
- Blood clot contraction: Mechanisms, pathophysiology, and disease.Research and practice in thrombosis and haemostasis · 2023Article
- INTEGRINS: A BEDSIDE TO BENCH TO BEDSIDE STORY.Transactions of the American Clinical and Climatological Association · 2023Article
- Upconversion nanoparticles regulated drug & gas dual-effective nanoplatform for the targeting cooperated therapy of thrombus and anticoagulation.Bioactive materials · 2022Article
- Effects of β2 Integrins on Osteoclasts, Macrophages, Chondrocytes, and Synovial Fibroblasts in Osteoarthritis.Biomolecules · 2022Review
- Article
- Targeting the RT loop of Src SH3 in Platelets Prevents Thrombosis without Compromising Hemostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
A prevailing dogma is that inhibition of vascular thrombosis by antagonizing platelet integrin αIIbβ3 cannot be achieved without compromising hemostasis, thus causing serious bleeding and increased morbidity and mortality. It is speculated that these adverse outcomes result from drug-induced activating conformational changes in αIIbβ3 but direct proof is lacking. Here, we report the structure-guided design of peptide Hr10 and a modified form of the partial agonist drug tirofiban that act as "pure" antagonists of αIIbβ3, i.e., they no longer induce the conformational changes in αIIbβ3. Both agents inhibit human platelet aggregation but preserve clot retraction. Hr10 and modified tirofiban are as effective as partial agonist drugs in inhibiting vascular thrombosis in humanized mice, but neither causes serious bleeding, establishing a causal link between partial agonism and impaired hemostasis. Pure orthosteric inhibitors of αIIbβ3 may thus provide safer alternatives for human therapy, and valuable tools to probe structure-activity relationships in integrins.
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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.