ArticleThe Journal of biological chemistry2011
Discovery of very late antigen-4 (VLA-4, alpha4beta1 integrin) allosteric antagonists.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Comparison of the efficacy of hematopoietic stem cell mobilization regimens: a systematic review and network meta-analysis of preclinical studies.Stem cell research & therapy · 2021Pooled it
- The evaluation of thioridazine as a hematopoietic progenitor cell mobilizing agent in healthy human subjects.Journal of clinical pharmacology · 2015Trial
- Butyrate Produced by Gut Microbiota Regulates Atherosclerosis: A Narrative Review of the Latest Findings.International journal of molecular sciences · 2025Review
- Focal adhesion in the tumour metastasis: from molecular mechanisms to therapeutic targets.Biomarker research · 2025Review
- A Flow Cytometry-Based High-Throughput Technique for Screening Integrin-Inhibitory Drugs.Journal of visualized experiments : JoVE · 2024Article
- Single-molecule characterization of subtype-specific β1 integrin mechanics.Nature communications · 2022Article
- Article
- CC16 Binding to αAmerican journal of respiratory and critical care medicine · 2021Article
- Visualization of integrin molecules by fluorescence imaging and techniques.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2021Article
- An integrated QSAR modeling approach to explore the structure-property and selectivity relationships of N-benzoyl-L-biphenylalanines as integrin antagonists.Molecular diversity · 2018Article
- Interleukin 17A Promotes Lymphocytes Adhesion and Induces CCL2 and CXCL1 Release from Brain Endothelial Cells.International journal of molecular sciences · 2017Article
- Integrin-based therapeutics: biological basis, clinical use and new drugs.Nature reviews. Drug discovery · 2016Review
- Mast cells and dendritic cells form synapses that facilitate antigen transfer for T cell activation.The Journal of cell biology · 2015Article
- Carbon monoxide down-regulates α4β1 integrin-specific ligand binding and cell adhesion: a possible mechanism for cell mobilization.BMC immunology · 2014Article
- Role of integrin alpha4 in drug resistance of leukemia.Frontiers in oncology · 2014Review
- Inverse cancer comorbidity: a serendipitous opportunity to gain insight into CNS disorders.Nature reviews. Neuroscience · 2013Review
- Flow cytometry enables a high-throughput homogeneous fluorescent antibody-binding assay for cytotoxic T cell lytic granule exocytosis.Journal of biomolecular screening · 2013Article
- Aspects of VLA-4 and LFA-1 regulation that may contribute to rolling and firm adhesion.Frontiers in immunology · 2012Article
- Is prolonged stem cell mobilization detrimental for hematopoiesis?Medical hypotheses · 2011Article
- Real-time analysis of the inside-out regulation of lymphocyte function-associated antigen-1 revealed similarities to and differences from very late antigen-4.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Integrins are cell adhesion receptors that mediate cell-to-cell, or cell-to-extracellular matrix adhesion. They represent an attractive target for treatment of multiple diseases. Two classes of small molecule integrin inhibitors have been developed. Competitive antagonists bind directly to the integrin ligand binding pocket and thus disrupt the ligand-receptor interaction. Allosteric antagonists have been developed primarily for α(L)β(2)- integrin (LFA-1, lymphocyte function-associated antigen-1). Here we present the results of screening the Prestwick Chemical Library using a recently developed assay for the detection of α(4)β(1)-integrin allosteric antagonists. Secondary assays confirmed that the compounds identified: 1) do not behave like competitive (direct) antagonists; 2) decrease ligand binding affinity for VLA-4 ∼2 orders of magnitude; 3) exhibit antagonistic properties at low temperature. In a cell based adhesion assay in vitro, the compounds rapidly disrupted cellular aggregates. In accord with reports that VLA-4 antagonists in vivo induce mobilization of hematopoietic progenitors into the peripheral blood, we found that administration of one of the compounds significantly increased the number of colony-forming units in mice. This effect was comparable to AMD3100, a well known progenitor mobilizing agent. Because all the identified compounds are structurally related, previously used, or currently marketed drugs, this result opens a range of therapeutic possibilities for VLA-4-related pathologies.
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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.