ArticleScientific reports2018
Identification of new EphA4 inhibitors by virtual screening of FDA-approved drugs.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- NRGSuite-Qt: a PyMOL plugin for high-throughput virtual screening, molecular docking, normal-mode analysis, the study of molecular interactions, and the detection of binding-site similarities.Bioinformatics advances · 2025Article
- An orally available compound suppresses glucagon hypersecretion and normalizes hyperglycemia in type 1 diabetes.JCI insight · 2024Article
- Unraveling the Potential of EphA4: A Breakthrough Target and Beacon of Hope for Neurological Diseases.Cellular and molecular neurobiology · 2023Review
- EphA4/EphrinB2 signaling mediates pericyte-induced transient glia limitans formation as a secondary protective barrier after subarachnoid hemorrhage in mice.Experimental neurology · 2023Article
- Drug repurposing for Alzheimer's disease from 2012-2022-a 10-year literature review.Frontiers in pharmacology · 2023Review
- Cholenic acid derivative UniPR1331 impairs tumor angiogenesis via blockade of VEGF/VEGFR2 in addition to Eph/ephrin.Cancer gene therapy · 2022Article
- An integrated chemo-informatics and in vitro experimental approach repurposes acarbose as a post-ischemic neuro-protectant.3 Biotech · 2022Article
- Optimization of Cavity-Based Negative Images to Boost Docking Enrichment in Virtual Screening.Journal of chemical information and modeling · 2022Article
- HeTDR: Drug repositioning based on heterogeneous networks and text mining.Patterns (New York, N.Y.) · 2021Article
- Roles and Mechanisms of Axon-Guidance Molecules in Alzheimer's Disease.Molecular neurobiology · 2021Review
- Nogo-A-Δ20/EphA4 interaction antagonizes apoptosis of neural stem cells by integrating p38 and JNK MAPK signaling.Journal of molecular histology · 2021Article
- DockingApp RF: A State-of-the-Art Novel Scoring Function for Molecular Docking in a User-Friendly Interface to AutoDock Vina.International journal of molecular sciences · 2020Article
- Identification of Small-Molecule Regulators of Testicular Receptor 4 via a Drug Repurposing Screening.ACS omega · 2020Article
- Genome-wide interaction analysis of pathological hallmarks in Alzheimer's disease.Neurobiology of aging · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The receptor tyrosine kinase, erythropoietin-producing hepatocellular A4 (EphA4), was recently identified as a molecular target for Alzheimer's disease (AD). We found that blockade of the interaction of the receptor and its ligands, ephrins, alleviates the disease phenotype in an AD transgenic mouse model, suggesting that targeting EphA4 is a potential approach for developing AD interventions. In this study, we identified five FDA-approved drugs-ergoloid, cyproheptadine, nilotinib, abiraterone, and retapamulin-as potential inhibitors of EphA4 by using an integrated approach combining virtual screening with biochemical and cellular assays. We initially screened a database of FDA-approved drugs using molecular docking against the ligand-binding domain of EphA4. Then, we selected 22 candidate drugs and examined their inhibitory activity towards EphA4. Among them, five drugs inhibited EphA4 clustering induced by ephrin-A in cultured primary neurons. Specifically, nilotinib, a kinase inhibitor, inhibited the binding of EphA4 and ephrin-A at micromolar scale in a dosage-dependent manner. Furthermore, nilotinib inhibited the activation of EphA4 and EphA4-dependent growth cone collapse in cultured hippocampal neurons, demonstrating that the drug exhibits EphA4 inhibitory activity in cellular context. As demonstrated in our combined computational and experimental approaches, repurposing of FDA-approved drugs to inhibit EphA4 may provide an alternative fast-track approach for identifying and developing new treatments for AD.
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