ArticlePloS one2014
Multi-kinase inhibitor C1 triggers mitotic catastrophe of glioma stem cells mainly through MELK kinase inhibition.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The trial behind it
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Trial
- Molecular insights into DNA damage response plasticity in glioma stem cells.Communications biology · 2026Review
- Maternal Embryonic Leucine Zipper Kinase (Biology · 2026Review
- Discovery of the MELK-Nucleostemin Axis in Glioblastoma: Implications for p53 Regulation and Tumor Progression.Journal of microbiology and biotechnology · 2026Article
- Targeting MELK in tumor cells and tumor microenvironment: from function and mechanism to therapeutic application.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Maternal Embryonic Leucine Zipper Kinase (MELK) as a Promising Therapeutic Target in Triple Negative Breast Cancer.Anti-cancer agents in medicinal chemistry · 2025Review
- The Effect of Therapy Regimen on Antitumor Efficacy of the Nanosomal Doxorubicin against Rat Glioblastoma 101.8.Bulletin of experimental biology and medicine · 2024Article
- MELK is a prognostic biomarker and correlated with immune infiltration in glioma.Frontiers in neurology · 2022Article
- Functional genomics for breast cancer drug target discovery.Journal of human genetics · 2021Review
- Enigmatic MELK: The controversy surrounding its complex role in cancer.The Journal of biological chemistry · 2020Review
- Mass spectrometry-based selectivity profiling identifies a highly selective inhibitor of the kinase MELK that delays mitotic entry in cancer cells.The Journal of biological chemistry · 2020Article
- MEK/MELK inhibition and blood-brain barrier deficiencies in atypical teratoid/rhabdoid tumors.Neuro-oncology · 2020Article
- Suppression of colorectal cancer cell growth by combined treatment of 6-gingerol and γ-tocotrienol via alteration of multiple signalling pathways.Journal of natural medicines · 2019Article
- Polo‑like kinase 4 promotes tumorigenesis and induces resistance to radiotherapy in glioblastoma.Oncology reports · 2019Article
- In silico discovery of a FOXM1 driven embryonal signaling pathway in therapy resistant neuroblastoma tumors.Scientific reports · 2018Article
- Elucidating the Role of the Maternal Embryonic Leucine Zipper Kinase in Adrenocortical Carcinoma.Endocrinology · 2018Article
- Article
- Divergent evolution of temozolomide resistance in glioblastoma stem cells is reflected in extracellular vesicles and coupled with radiosensitization.Neuro-oncology · 2018Article
- Targeting dual specificity protein kinase TTK attenuates tumorigenesis of glioblastoma.Oncotarget · 2018Article
- Maternal embryonic leucine zipper kinase inhibits epithelial-mesenchymal transition by regulating transforming growth factor-β signaling.Oncology letters · 2017Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
Glioblastoma multiforme (GBM) is a highly lethal brain tumor. Due to resistance to current therapies, patient prognosis remains poor and development of novel and effective GBM therapy is crucial. Glioma stem cells (GSCs) have gained attention as a therapeutic target in GBM due to their relative resistance to current therapies and potent tumor-initiating ability. Previously, we identified that the mitotic kinase maternal embryonic leucine-zipper kinase (MELK) is highly expressed in GBM tissues, specifically in GSCs, and its expression is inversely correlated with the post-surgical survival period of GBM patients. In addition, patient-derived GSCs depend on MELK for their survival and growth both in vitro and in vivo. Here, we demonstrate evidence that the role of MELK in the GSC survival is specifically dependent on its kinase activity. With in silico structure-based analysis for protein-compound interaction, we identified the small molecule Compound 1 (C1) is predicted to bind to the kinase-active site of MELK protein. Elimination of MELK kinase activity was confirmed by in vitro kinase assay in nano-molar concentrations. When patient-derived GSCs were treated with C1, they underwent mitotic arrest and subsequent cellular apoptosis in vitro, a phenotype identical to that observed with shRNA-mediated MELK knockdown. In addition, C1 treatment strongly induced tumor cell apoptosis in slice cultures of GBM surgical specimens and attenuated growth of mouse intracranial tumors derived from GSCs in a dose-dependent manner. Lastly, C1 treatment sensitizes GSCs to radiation treatment. Collectively, these data indicate that targeting MELK kinase activity is a promising approach to attenuate GBM growth by eliminating GSCs in tumors.
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