ArticleJournal of experimental & clinical cancer research : CR2019
A selective c-Met and Trks inhibitor Indo5 suppresses hepatocellular carcinoma growth.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Activation of Nerve Growth Factor signaling limits the response to lenvatinib in hepatocellular carcinoma.Signal transduction and targeted therapy · 2026Article
- Immunotherapy targeting liver cancer tumor-initiating cells: challenges, mechanisms, and emerging therapeutic horizons.Frontiers in immunology · 2025Review
- Bioactive Products Targeting C-Met As Potential Antitumour Drugs.Anti-cancer agents in medicinal chemistry · 2025Review
- Mitoepigenetics pathways and natural compounds: a dual approach to combatting hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2024Review
- Review
- Nerve Growth Factor and the Role of Inflammation in Tumor Development.Current issues in molecular biology · 2024Review
- A novel c-Met/TRK inhibitor 1D228 efficiently inhibits tumor growth by targeting angiogenesis and tumor cell proliferation.Cell death & disease · 2023Article
- Anti-cancer therapeutic strategies based on HGF/MET, EpCAM, and tumor-stromal cross talk.Cancer cell international · 2022Review
- Selenium sulfide disrupts the PLAGL2/C-MET/STAT3-induced resistance against mitochondrial apoptosis in hepatocellular carcinoma.Clinical and translational medicine · 2021Article
- The mir-423-5p/MMP-2 Axis Regulates the Nerve Growth Factor-Induced Promotion of Chondrosarcoma Metastasis.Cancers · 2021Article
- Critical signaling pathways governing hepatocellular carcinoma behavior; small molecule-based approaches.Cancer cell international · 2021Review
- Nerve growth factor regulates liver cancer cell polarity and motility.Molecular medicine reports · 2021Article
- Preclinical Pharmacokinetics, Tissue Distribution, and Primary Safety Evaluation of Indo5, a Novel Selective Inhibitor of c-Met and Trks.Frontiers in pharmacology · 2021Article
- Spectrum of Mesenchymal-Epithelial Transition Aberrations and Potential Clinical Implications: Insights From Integrative Pancancer Analysis.Frontiers in oncology · 2020Article
- Identification of P-Rex1 in the Regulation of Liver Cancer Cell Proliferation and Migration via HGF/c-Met/Akt Pathway.OncoTargets and therapy · 2020Article
- The Function of the HGF/c-Met Axis in Hepatocellular Carcinoma.Frontiers in cell and developmental biology · 2020Review
- Design, Synthesis, and Biological Evaluation of Pyridineamide Derivatives Containing a 1,2,3-Triazole Fragment as Type II c-Met Inhibitors.Molecules (Basel, Switzerland) · 2019Article
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Authors and funding
15 authors.
Funding
Abstract
backgroundHuman hepatocellular carcinoma (HCC) lacks effective curative therapy and there is an urgent need to develop a novel molecular-targeted therapy for HCC. Selective tyrosine kinase inhibitors have shown promise in treating cancers including HCC. Tyrosine kinases c-Met and Trks are potential therapeutic targets of HCC and strategies to interrupt c-Met and Trks cross-signaling may result in increased effects on HCC inhibition.
methodsThe effects of Indo5 on c-Met and Trks activity were determined with in vitro kinase activity assay, cell-based signaling pathway activation, and kinases-driven cell transformation. The in vivo anti-tumor activity was determined with xenograft mice and liver orthotopic mice models. The co-expression of c-Met and TrkB in 180 pairs of HCC and adjacent normal tissues were detected using immunohistochemical staining.
resultsIndo5, a novel lead compound displayed biochemical potency against both c-Met and Trks with selectivity over 13 human kinases. Indo5 abrogated HGF-induced c-Met signaling activation and BDNF/NGF-induced Trks signal activation, c-Met or TrkB-mediated cell transformation and migration. Furthermore, Indo5 significantly decreased the growth of HCC cells in xenograft mice and improved the survival of mice with liver orthotopic tumors. In addition, co-expression of c-Met and TrkB in HCC patients was a predictor of poor prognosis, and combined inhibition of c-Met and TrkB exerted a synergistic suppressive effect on HCC.
conclusionsThese findings indicate that Indo5 is associated with marked suppression of c-Met and Trks co-expressing HCC, supporting its clinical development as an antitumor treatment for HCC patients with co-active c-Met and Trks signaling.
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