ArticleEuropean journal of medicinal chemistry2018
Design and synthesis of small molecule agonists of EphA2 receptor.
Article in European journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- The Vap33 signaling axis precisely coordinates the timing of motoneuron dendritogenesis in neural map development.Nature communications · 2025Article
- Eph receptor signaling complexes in the plasma membrane.Trends in biochemical sciences · 2024Review
- EphA2 in Cancer: Molecular Complexity and Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- Unveiling the therapeutic promise of EphA2 in glioblastoma: a comprehensive review.Discover oncology · 2024Review
- Regioselective quinazoline C2 modifications through the azide-tetrazole tautomeric equilibrium.Beilstein journal of organic chemistry · 2024Article
- Optimization of the Lead Compound NVP-BHG712 as a Colorectal Cancer Inhibitor.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- Targefrin: A Potent Agent Targeting the Ligand Binding Domain of EphA2.Journal of medicinal chemistry · 2022Article
- Effective Tumor Targeting by EphA2-Agonist-Biotin-Streptavidin Conjugates.Molecules (Basel, Switzerland) · 2021Article
- Structure of the EphB6 receptor ectodomain.PloS one · 2021Article
- RETRACTED: Prostate Cancer Metastases Are Strongly Inhibited by Agonistic Epha2 Ligands in an Orthotopic Mouse Model.Cancers · 2020Article
- Dimeric small molecule agonists of EphA2 receptor inhibit glioblastoma cell growth.Bioorganic & medicinal chemistry · 2020Article
- Approaches to Manipulate Ephrin-A:EphA Forward Signaling Pathway.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Therapeutic Targeting of Pancreatic Cancer via EphA2 Dimeric Agonistic Agents.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Adaptive RSK-EphA2-GPRC5A signaling switch triggers chemotherapy resistance in ovarian cancer.EMBO molecular medicine · 2020Article
- A quantitative LC-MS/MS method for determination of a small molecule agonist of EphA2 in mouse plasma and brain tissue.Biomedical chromatography : BMC · 2019Article
- Therapeutic potential of targeting the Eph/ephrin signaling complex.The international journal of biochemistry & cell biology · 2018Review
- Structure-Based Design of Novel EphA2 Agonistic Agents with Nanomolar Affinity in Vitro and in Cell.ACS chemical biology · 2018Article
- EphA2 receptor is a key player in the metastatic onset of Ewing sarcoma.International journal of cancer · 2018Article
- Reduction of Circulating Cancer Cells and Metastases in Breast-Cancer Models by a Potent EphA2-Agonistic Peptide-Drug Conjugate.Journal of medicinal chemistry · 2018Article
- Structure-based analysis of curcumin and conventionaldrugs targeting tumor-inducing protein PHF20.Bioinformation · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Ligand-independent activation of EphA2 receptor kinase promotes cancer metastasis and invasion. Activating EphA2 receptor tyrosine kinase with small molecule agonist is a novel strategy to treat EphA2 overexpressing cancer. In this study, we performed a lead optimization of a small molecule Doxazosin that was identified as an EphA2 receptor agonist. 33 new analogs were developed and evaluated; a structure-activity relationship was summarized based on the EphA2 activation of these derivatives. Two new derivative compounds 24 and 27 showed much improved activity compared to Doxazosin. Compound 24 possesses a bulky amide moiety, and compound 27 has a dimeric structure that is very different to the parental compound. Compound 27 with a twelve-carbon linker of the dimer activated the kinase and induced receptor internalization and cell death with the best potency. Another dimer with a six-carbon linker has significantly reduced potency compared to the dimer with a longer linker, suggesting that the length of the linker is critical for the activity of the dimeric agonist. To explore the receptor binding characteristics of the new molecules, we applied a docking study to examine how the small molecule binds to the EphA2 receptor. The results reveal that compounds 24 and 27 form more hydrogen bonds to EphA2 than Doxazosin, suggesting that they may have higher binding affinity to the receptor.
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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.