ArticlePloS one2012
Direct and allosteric inhibition of the FGF2/HSPGs/FGFR1 ternary complex formation by an antiangiogenic, thrombospondin-1-mimic small molecule.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
23 citing papers in PubMed, 40 citations in OpenAlex.
- Synthetic Heparan Sulfate-like Oligosaccharides as Tools to Decipher Growth Factor Recognition.Journal of medicinal chemistry · 2026Article
- In Silico Screening and Anticancer-Apoptotic Evaluation of Newly Synthesized Thienopyrimidine/Sulfonamide Hybrids.International journal of molecular sciences · 2023Article
- Structural insights into regulation of CCN protein activities and functions.Journal of cell communication and signaling · 2023Review
- 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
- Fatty Acids, CD36, Thrombospondin-1, and CD47 in Glioblastoma: Together and/or Separately?International journal of molecular sciences · 2022Review
- Article
- Synthesis of Novel Suramin Analogs With Anti-Proliferative ActivityFrontiers in chemistry · 2021Article
- Allosteric Mechanisms of Nonadditive Substituent Contributions to Protein-Ligand Binding.Biophysical journal · 2020Article
- 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
- FGF2: a novel druggable target for glioblastoma?Expert opinion on therapeutic targets · 2020Review
- Heparin Binding Proteins as Therapeutic Target: An Historical Account and Current Trends.Medicines (Basel, Switzerland) · 2019Review
- Diabetes Impairs Angiogenesis and Induces Endothelial Cell Senescence by Up-Regulating Thrombospondin-CD47-Dependent Signaling.International journal of molecular sciences · 2019Article
- 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
- The Long Pentraxin 3 Plays a Role in Bone Turnover and Repair.Frontiers in immunology · 2018Article
- Integrating computational and chemical biology tools in the discovery of antiangiogenic small molecule ligands of FGF2 derived from endogenous inhibitors.Scientific reports · 2016Article
- Original insights on thrombospondin-1-related antireceptor strategies in cancer.Frontiers in pharmacology · 2015Review
- Cooperative structure of the heterotrimeric pre-mRNA retention and splicing complex.Nature structural & molecular biology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibroblast growth factors (FGFs) are recognized targets for the development of therapies against angiogenesis-driven diseases, including cancer. The formation of a ternary complex with the transmembrane tyrosine kinase receptors (FGFRs), and heparan sulphate proteoglycans (HSPGs) is required for FGF2 pro-angiogenic activity. Here by using a combination of techniques including Nuclear Magnetic Resonance, Molecular Dynamics, Surface Plasmon Resonance and cell-based binding assays we clarify the molecular mechanism of inhibition of an angiostatic small molecule, sm27, mimicking the endogenous inhibitor of angiogenesis, thrombospondin-1. NMR and MD data demonstrate that sm27 engages the heparin-binding site of FGF2 and induces long-range dynamics perturbations along FGF2/FGFR1 interface regions. The functional consequence of the inhibitor binding is an impaired FGF2 interaction with both its receptors, as demonstrated by SPR and cell-based binding assays. We propose that sm27 antiangiogenic activity is based on a twofold-direct and allosteric-mechanism, inhibiting FGF2 binding to both its receptors.
Indexed as
Identifiers
What OpenQuestion holds
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.