ArticleInvestigational new drugs2014
The novel kinase inhibitor EMD1214063 is effective against neuroblastoma.
Article in Investigational new drugs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Systematic review of the receptor tyrosine kinase superfamily in neuroblastoma pathophysiology.Cancer metastasis reviews · 2022Pooled it
- Hepatocyte growth factor/c-Met signaling axis in human diseases: Mechanistic insights and therapeutic potential.Journal of cell communication and signaling · 2026Review
- Advances in Targeting Growth Factor Signalling in Neuroblastoma and Overcoming Drug Resistance.Cells · 2025Review
- Fibroblast growth factor receptor alterations and resistance mechanisms in the treatment of pediatric solid tumors.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Repurposing of c-MET Inhibitor Tivantinib Inhibits Pediatric Neuroblastoma Cellular Growth.Pharmaceuticals (Basel, Switzerland) · 2024Article
- The Preclinical Pharmacology of Tepotinib-A Highly Selective MET Inhibitor with Activity in Tumors Harboring MET Alterations.Molecular cancer therapeutics · 2023Review
- The hepatocyte growth factor/mesenchymal epithelial transition factor axis in high-risk pediatric solid tumors and the anti-tumor activity of targeted therapeutic agents.Frontiers in pediatrics · 2022Review
- Mesenchymal Epithelial Transition Factor Signaling in Pediatric Nervous System Tumors: Implications for Malignancy and Cancer Stem Cell Enrichment.Frontiers in cell and developmental biology · 2021Review
- Mechanisms of Efficacy of the FGFR1-3 Inhibitor AZD4547 in Pediatric Solid Tumor Models.Investigational new drugs · 2020Article
- Open-label, single-center, phase I trial to investigate the mass balance and absolute bioavailability of the highly selective oral MET inhibitor tepotinib in healthy volunteers.Investigational new drugs · 2020Article
- Regorafenib is effective against neuroblastoma in vitro and in vivo and inhibits the RAS/MAPK, PI3K/Akt/mTOR and Fos/Jun pathways.British journal of cancer · 2020Article
- MET exon 14 juxtamembrane splicing mutations: clinical and therapeutical perspectives for cancer therapy.Annals of translational medicine · 2017Review
- The novel kinase inhibitor ponatinib is an effective anti-angiogenic agent against neuroblastoma.Investigational new drugs · 2016Article
- Nifurtimox Is Effective Against Neural Tumor Cells and Is Synergistic with Buthionine Sulfoximine.Scientific reports · 2016Article
- A Polymorphism in the FGFR4 Gene Is Associated With Risk of Neuroblastoma and Altered Receptor Degradation.Journal of pediatric hematology/oncology · 2016Article
- Neuroblastoma patient outcomes, tumor differentiation, and ERK activation are correlated with expression levels of the ubiquitin ligase UBE4B.Genes & cancer · 2016Article
- The hepatocyte growth factor receptor as a potential therapeutic target for dedifferentiated liposarcoma.Laboratory investigation; a journal of technical methods and pathology · 2015Article
- Small-molecule inhibitors of the receptor tyrosine kinases: promising tools for targeted cancer therapies.International journal of molecular sciences · 2014Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChildren with high-risk neuroblastoma have poor survival rates, and novel therapies are needed. Previous studies have identified a role for the HGF/c-Met pathway in neuroblastoma pathogenesis. We hypothesized that EMD1214063 would be effective against neuroblastoma tumor cells and tumors in preclinical models via inhibition of HGF/c-Met signaling. Methods We determined the expression of c-Met protein by Western blots in a panel of neuroblastoma tumor cell lines and neuroblastoma cell viability after treatment with EMD1214063 using MTT assays. TUNEL assays and assays for DNA ladder formation, were performed to measure the induction of apoptosis after EMD1214063 treatment. Inhibition of intracellular signaling was measured by Western blot analysis of treated and untreated cells. To investigate the efficacy of EMD1214063 against neuroblastoma tumors in vivo, neuroblastoma cells were injected orthotopically into immunocompromised mice, and mice were treated with oral EMD1214063. Tumors were evaluated for growth, histologic appearance, and induction of apoptosis by immunohistochemistry. Results All neuroblastoma cell lines were sensitive to EMD1214063, and IC50 values ranged from 2.4 to 8.5 μM. EMD1214063 treatment inhibited HGF-mediated c-Met phosphorylation and MEK phosphorylation in neuroblastoma cells. EMD1214063 induced apoptosis in all tested cell lines. In mice with neuroblastoma xenograft tumors, EMD1214063 treatment reduced tumor growth. Conclusions Treatment of neuroblastoma tumor cells with EMD1214063 inhibits HGF-induced c-Met phosphorylation and results in cell death. EMD1214063 treatment is also effective in reducing tumor growth in vivo. EMD1214063 therefore represents a novel therapeutic agent for neuroblastoma, and further preclinical studies of EMD1214063 are warranted.
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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.