ArticleThe Journal of biological chemistry2012
Novel α2β1 integrin inhibitors reveal that integrin binding to collagen under shear stress conditions does not require receptor preactivation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- Engineering scalable vascularized kidney organoids for in vivo glomerular filtration with human endothelial integration.npj biomedical innovations · 2026Article
- COL6A2 drives clear cell renal cell carcinoma progression via integrin-dependent modulation of Wnt/β-catenin signaling.Journal of Cancer · 2025Article
- α2β1 Integrin specific inhibitor BTT-3033 promotes paclitaxel-induced apoptosis in human ovarian cancer cells.Research in pharmaceutical sciences · 2024Article
- Laminin-derived peptide, IKVAV, modulates macrophage phenotype through integrin mediation.Matrix biology plus · 2024Article
- Integrin β1 is a key determinant of the expression of angiotensin-converting enzyme 2 (ACE2) in the kidney epithelial cells.European journal of cell biology · 2023Article
- VGLL3 is a mechanosensitive protein that promotes cardiac fibrosis through liquid-liquid phase separation.Nature communications · 2023Article
- Truncated O-Glycan-Bearing MUC16 Enhances Pancreatic Cancer Cells Aggressiveness via α4β1 Integrin Complexes and FAK Signaling.International journal of molecular sciences · 2022Article
- Perspectives on pediatric congenital aortic valve stenosis: Extracellular matrix proteins, post translational modifications, and proteomic strategies.Frontiers in cardiovascular medicine · 2022Review
- Integrin activation is an essential component of SARS-CoV-2 infection.Scientific reports · 2021Article
- Phosphoproteomics identifies potential downstream targets of the integrin α2β1 inhibitor BTT-3033 in prostate stromal cells.Annals of translational medicine · 2021Article
- Article
- Collagen I Fibrous Substrates Modulate the Proliferation and Secretome of Estrogen Receptor-Positive Breast Tumor Cells in a Hormone-Restricted Microenvironment.ACS biomaterials science & engineering · 2021Article
- Flow studies on human GPVI-deficient blood under coagulating and noncoagulating conditions.Blood advances · 2020Article
- Investigation of Cancer Cell Migration and Proliferation on Synthetic Extracellular Matrix Peptide Hydrogels.Frontiers in bioengineering and biotechnology · 2020Article
- Integrins as therapeutic targets in the organ-specific metastasis of human malignant melanoma.Journal of experimental & clinical cancer research : CR · 2018Review
- Integrin α2β1 in nonactivated conformation can induce focal adhesion kinase signaling.Scientific reports · 2017Article
- Article
- Cellular Biomechanics in Drug Screening and Evaluation: Mechanopharmacology.Trends in pharmacological sciences · 2016Review
- TNF-α-stimulated fibroblasts secrete lumican to promote fibrocyte differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The interaction between α2β1 integrin (GPIa/IIa, VLA-2) and vascular collagen is one of the initiating events in thrombus formation. Here, we describe two structurally similar sulfonamide derivatives, BTT-3033 and BTT-3034, and show that, under static conditions, they have an almost identical effect on α2-expressing CHO cell adhesion to collagen I, but only BTT-3033 blocks platelet attachment under flow (90 dynes/cm(2)). Differential scanning fluorimetry showed that both molecules bind to the α2I domain of the recombinant α2 subunit. To further study integrin binding mechanism(s) of the two sulfonamides, we created an α2 Y285F mutant containing a substitution near the metal ion-dependent adhesion site motif in the α2I domain. The action of BTT-3033, unlike that of BTT-3034, was dependent on Tyr-285. In static conditions BTT-3034, but not BTT-3033, inhibited collagen binding by an α2 variant carrying a conformationally activating E318W mutation. Conversely, in under flow conditions (90 dynes/cm(2)) BTT-3033, but not BTT-3034, inhibited collagen binding by an α2 variant expressing E336A loss-of-function mutation. Thus, the binding sites for BTT-3033 and BTT-3034 are differentially available in distinct integrin conformations. Therefore, these sulfonamides can be used to study the biological role of different functional stages of α2β1. Furthermore, only the inhibitor that recognized the non-activated conformation of α2β1 integrin under shear stress conditions effectively blocked platelet adhesion, suggesting that the initial interaction between integrin and collagen takes place prior to receptor activation.
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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.