ArticleBlood advances2023
Targeting platelet GPVI with glenzocimab: a novel mechanism for inhibition.
Article in Blood advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 34 citations in OpenAlex.
- Trial
- Targeting GPVI with glenzocimab in COVID-19 patients: Results from a randomized clinical trial.PloS one · 2024Trial
- Partial downregulation of platelet glycoprotein VI by low affinity antibodies confers sustained and safe antithrombotic protection.Signal transduction and targeted therapy · 2026Article
- Platelet-Collagen Interactions in Hemostatic Mechanisms.Advanced healthcare materials · 2026Review
- Receptor homodimerization significantly prolongs the lifetime of ligand-induced cross-linking of CLEC-2 but not GPVI.Blood vessels, thrombosis & hemostasis · 2026Article
- Glycoprotein VI is a receptor for the PF4/anti-PF4 IgG complex and contributes to platelet activation in heparin-induced thrombocytopenia (HIT).Journal of thrombosis and haemostasis : JTH · 2025Article
- Glycoprotein VI inhibitors: glenzocimab and EMA601 two inhibitory Fabs.European heart journal · 2025Article
- GPVI-mediated thrombus stabilization of shear-induced platelet aggregates in a microfluidic stenosis.Biophysical journal · 2025Article
- Platelet Pathophysiology: Unexpected New Research Directions.Seminars in thrombosis and hemostasis · 2024Article
- Soluble glycoprotein VI predicts abdominal aortic aneurysm growth rate and is a novel therapeutic target.Blood · 2024Article
- Functional characterization of a nanobody-based glycoprotein VI-specific platelet agonist.Research and practice in thrombosis and haemostasis · 2024Article
- GPVI inhibition: Advancing antithrombotic therapy in cardiovascular disease.European heart journal. Cardiovascular pharmacotherapy · 2024Review
- Affimer reagents as tool molecules to modulate platelet GPVI-ligand interactions and specifically bind GPVI dimer.Blood advances · 2024Article
- The interaction of platelet-related factors with tumor cells promotes tumor metastasis.Journal of translational medicine · 2024Review
- Differential Proteoglycan Expression in Atherosclerosis Alters Platelet Adhesion and Activation.International journal of molecular sciences · 2024Article
- Protease-activated receptors and glycoprotein VI cooperatively drive the platelet component in thromboelastography.Journal of thrombosis and haemostasis : JTH · 2023Article
- Pro-Tumorigenic and Thrombotic Activities of Platelets in Lung Cancer.International journal of molecular sciences · 2023Review
- The Contribution of Vascular Proteoglycans to Atherothrombosis: Clinical Implications.International journal of molecular sciences · 2023Review
- Minimal Collagen-Binding Epitope of Glycoprotein VI in Human and Mouse Platelets.Biomedicines · 2023Article
- Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis.Frontiers in pharmacology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
Abstract
Platelet glycoprotein VI (GPVI) is attracting interest as a potential target for the development of new antiplatelet molecules with a low bleeding risk. GPVI binding to vascular collagen initiates thrombus formation and GPVI interactions with fibrin promote the growth and stability of the thrombus. In this study, we show that glenzocimab, a clinical stage humanized antibody fragment (Fab) with a high affinity for GPVI, blocks the binding of both ligands through a combination of steric hindrance and structural change. A cocrystal of glenzocimab with an extracellular domain of monomeric GPVI was obtained and its structure determined to a resolution of 1.9 Å. The data revealed that (1) glenzocimab binds to the D2 domain of GPVI, GPVI dimerization was not observed in the crystal structure because glenzocimab prevented D2 homotypic interactions and the formation of dimers that have a high affinity for collagen and fibrin; and (2) the light variable domain of the GPVI-bound Fab causes steric hindrance that is predicted to prevent the collagen-related peptide (CRP)/collagen fibers from extending out of their binding site and preclude GPVI clustering and downstream signaling. Glenzocimab did not bind to a truncated GPVI missing loop residues 129 to 136, thus validating the epitope identified in the crystal structure. Overall, these findings demonstrate that the binding of glenzocimab to the D2 domain of GPVI induces steric hindrance and structural modifications that drive the inhibition of GPVI interactions with its major ligands.
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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.