ArticleBiochemical pharmacology2013
Design, synthesis and characterization of novel small molecular inhibitors of ephrin-B2 binding to EphB4.
Article in Biochemical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Article
- Manipulating the EphB4-ephrinB2 axis to reduce metastasis in HNSCC.bioRxiv : the preprint server for biology · 2024Article
- Eph Receptors in Cancer.Biomedicines · 2023Review
- The critical role of the interplays of EphrinB2/EphB4 and VEGF in the induction of angiogenesis.Molecular biology reports · 2020Review
- Essential roles of EphrinB2 in mammalian heart: from development to diseases.Cell communication and signaling : CCS · 2019Review
- EphB4: A promising target for upper aerodigestive malignancies.Biochimica et biophysica acta. Reviews on cancer · 2018Review
- Inhibition of angiogenesis by leflunomide via targeting the soluble ephrin-A1/EphA2 system in bladder cancer.Scientific reports · 2018Article
- Targeting the Eph System with Peptides and Peptide Conjugates.Current drug targets · 2015Review
- Eph receptors and ephrins: therapeutic opportunities.Annual review of pharmacology and toxicology · 2015Review
- Ephrin B2/EphB4 mediates the actions of IGF-I signaling in regulating endochondral bone formation.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2014Article
- Druggable orthosteric and allosteric hot spots to target protein-protein interactions.Current pharmaceutical design · 2014Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
EphB4 is a member of the large Eph receptor tyrosine kinase family. By interacting with its preferred ligand ephrin-B2, which is also a transmembrane protein, EphB4 plays a role in a variety of physiological and pathological processes ranging from bone remodeling to cancer malignancy. EphB4-ephrin-B2 binding occurs at sites of contact between cells. Ephrin-B2 causes EphB4 clustering and increased kinase activity to generate downstream signals that affect cell behavior. Previous work identified a high-affinity antagonistic peptide that targets EphB4, named TNYL-RAW. This peptide is 15 amino acid long, has a molecular weight of ~1700 Da and binds to the ephrin-binding pocket of EphB4. Here we report the structure-based design and chemical synthesis of two novel small molecules of ~600-700 Da, which were designed starting from the small and functionally critical C-terminal portion of the TNYL-RAW peptide. These compounds inhibit ephrin-B2 binding to EphB4 at low micromolar concentrations. Additionally, although the ephrin-B2 ligand can interacts with multiple other Eph receptors besides EphB4, the two compounds retain the high selectivity of the TNYL-RAW peptide in targeting EphB4. TNYL-RAW peptide displacement experiments using the more potent of the two compounds, compound 5, suggest a competitive mode of inhibition. These EphB4 antagonistic compounds can serve as promising templates for the further development of small molecule drugs targeting EphB4.
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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.