Tuesday, November 6, 2018

#Inhibition of CK1 affects Viability and Survival of #GlioblastomaCells by Joachim Bischof in BJSTR

Abstract

#Glioblastomamultiforme (GBM) is the most common and lethal primary brain tumor with an inevitable fatal outcome. However, the complex network of #dysregulatedpathways in #glioblastoma development and progression remains to be poorly understood. Consequently, novel approaches for the treatment of glioblastoma are seriously needed and the search for new target molecules for #pharmacologicinterventionis in the focus of research. Since it is known that CK1 isoforms are involved in Wnt/β-catenin and sonic hedgehog signal transduction pathways, which are often dysregulated in glioblastoma cells, inhibition of CK1 isoforms might hold therapeutic potential. Therefore, two previously characterized CK1 isoform-selective #difluoro-dioxolo-benzoimidazole derivatives were investigated on their effects on the viability of glioblastoma cell lines. Compound 2 showed major effects on the tested cells with EC50 values below 100 nM in most of the analyzed #glioblastomacell lines. Cell cycle analyses underlined the observation that compound 2 is most effective since treatment with compound 2 induced cell death in up to 57% of the analyzed cells. In conclusion, our data point to a high therapeutic potential of CK1 isoform-selective inhibitors for the treatment of glioblastoma.




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