ArticleThe Journal of biological chemistry2010
Non-peptidic thrombospondin-1 mimics as fibroblast growth factor-2 inhibitors: an integrated strategy for the development of new antiangiogenic compounds.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 73 citations in OpenAlex.
- Review
- TSP-1 interaction with RANK and OPG: implications for bone remodeling and osteolytic bone metastasis.Cell death & disease · 2026Article
- Inhibition of FGFR Signaling by Targeting FGF/FGFR Extracellular Interactions: Towards the Comprehension of the Molecular Mechanism through NMR Approaches.International journal of molecular sciences · 2022Article
- New developments in the biology of fibroblast growth factors.WIREs mechanisms of disease · 2022Review
- Article
- Fatty Acids, CD36, Thrombospondin-1, and CD47 in Glioblastoma: Together and/or Separately?International journal of molecular sciences · 2022Review
- Advances in Anti-metabolic Disease Treatments Targeting CD47.Current pharmaceutical design · 2022Review
- Endothelial Cell Behavior Is Determined by Receptor Clustering Induced by Thrombospondin-1.Frontiers in cell and developmental biology · 2021Review
- FGF/FGFR signaling in health and disease.Signal transduction and targeted therapy · 2020Review
- Small Ones to Fight a Big Problem-Intervention of Cancer Metastasis by Small Molecules.Cancers · 2020Review
- Synergy Between Low Dose Metronomic Chemotherapy and the pH-centered Approach Against Cancer.International journal of molecular sciences · 2019Review
- Interferon-Tau Exerts Direct Prosurvival and Antiapoptotic Actions in Luteinized Bovine Granulosa Cells.Scientific reports · 2019Article
- Heparin Binding Proteins as Therapeutic Target: An Historical Account and Current Trends.Medicines (Basel, Switzerland) · 2019Review
- Thrombospondin-1 in ocular surface health and disease.The ocular surface · 2019Review
- New Insights Into Implementation of Mesenchymal Stem Cells in Cancer Therapy: Prospects for Anti-angiogenesis Treatment.Frontiers in oncology · 2019Review
- Targeting Difficult Protein-Protein Interactions with Plain and General Computational Approaches.Molecules (Basel, Switzerland) · 2018Review
- Integration of pro- and anti-angiogenic signals by endothelial cells.Journal of cell communication and signaling · 2018Review
- Conversion of Protein Active Regions into Peptidomimetic Therapeutic Leads Using Backbone Cyclization and Cycloscan - How to Do it Yourself!Current topics in medicinal chemistry · 2018Review
- Novel PARP-1 Inhibitor Scaffolds Disclosed by a Dynamic Structure-Based Pharmacophore Approach.PloS one · 2017Article
- Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
Endogenous inhibitors of angiogenesis, such as thrombospondin-1 (TSP-1), are promising sources of therapeutic agents to treat angiogenesis-driven diseases, including cancer. TSP-1 regulates angiogenesis through different mechanisms, including binding and sequestration of the angiogenic factor fibroblast growth factor-2 (FGF-2), through a site located in the calcium binding type III repeats. We hypothesized that the FGF-2 binding sequence of TSP-1 might serve as a template for the development of inhibitors of angiogenesis. Using a peptide array approach followed by binding assays with synthetic peptides and recombinant proteins, we identified a FGF-2 binding sequence of TSP-1 in the 15-mer sequence DDDDDNDKIPDDRDN. Molecular dynamics simulations, taking the full flexibility of the ligand and receptor into account, and nuclear magnetic resonance identified the relevant residues and conformational determinants for the peptide-FGF interaction. This information was translated into a pharmacophore model used to screen the NCI2003 small molecule databases, leading to the identification of three small molecules that bound FGF-2 with affinity in the submicromolar range. The lead compounds inhibited FGF-2-induced endothelial cell proliferation in vitro and affected angiogenesis induced by FGF-2 in the chicken chorioallantoic membrane assay. These small molecules, therefore, represent promising leads for the development of antiangiogenic agents. Altogether, this study demonstrates that new biological insights obtained by integrated multidisciplinary approaches can be used to develop small molecule mimics of endogenous proteins as therapeutic agents.
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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.