Compounds > n4-(2-2-dimethyl-3-oxo-4h-pyrid(1-4)oxazin-6-yl)-5-fluoro-n2-(3-4-5-trimethoxyphenyl)-2-4-pyrimidinediamine

n4-(2-2-dimethyl-3-oxo-4h-pyrid(1-4)oxazin-6-yl)-5-fluoro-n2-(3-4-5-trimethoxyphenyl)-2-4-pyrimidinediamine and Glioblastoma

n4-(2-2-dimethyl-3-oxo-4h-pyrid(1-4)oxazin-6-yl)-5-fluoro-n2-(3-4-5-trimethoxyphenyl)-2-4-pyrimidinediamine has been researched along with Glioblastoma* in 1 studies

Other Studies

1 other study(ies) available for n4-(2-2-dimethyl-3-oxo-4h-pyrid(1-4)oxazin-6-yl)-5-fluoro-n2-(3-4-5-trimethoxyphenyl)-2-4-pyrimidinediamine and Glioblastoma

Article	Year
R406 elicits anti-Warburg effect via Syk-dependent and -independent mechanisms to trigger apoptosis in glioma stem cells. Cell death & disease, 2019, 05-01, Volume: 10, Issue:5 Given that glioma stem cells (GSCs) play a critical role in the initiation and chemoresistance in glioblastoma multiforme (GBM), targeting GSCs is an attractive strategy to treat GBM. Utilizing an anti-cancer compound library, we identified R406, the active metabolite of a FDA-approved Syk inhibitor for immune thrombocytopenia (ITP), with remarkable cytotoxicity against GSCs but not normal neural stem cells. R406 significantly inhibited neurosphere formation and triggered apoptosis in GSCs. R406 induced a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS) and subsequently production of excess ROS in GSCs. R406 also diminished tumor growth and efficiently sensitized gliomas to temozolomide in GSC-initiating xenograft mouse models. Mechanistically, the anti-GSC effect of R406 was due to the disruption of Syk/PI3K signaling in Syk-positive GSCs and PI3K/Akt pathway in Syk-negative GSCs respectively. Overall, these findings not only identify R406 as a promising GSC-targeting agent but also reveal the important role of Syk and PI3K pathways in the regulation of energy metabolism in GSCs. Topics: Animals; Antineoplastic Agents; Apoptosis; Brain Neoplasms; Cell Adhesion; Drug Resistance, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Glioblastoma; Glycolysis; Humans; Mice, Nude; Neoplastic Stem Cells; Oxazines; Oxidative Phosphorylation; Phosphatidylinositol 3-Kinases; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Pyridines; Signal Transduction; Survival Analysis; Syk Kinase; Temozolomide; Xenograft Model Antitumor Assays	2019

Article

Year

R406 elicits anti-Warburg effect via Syk-dependent and -independent mechanisms to trigger apoptosis in glioma stem cells.

Cell death & disease, 2019, 05-01, Volume: 10, Issue:5

Given that glioma stem cells (GSCs) play a critical role in the initiation and chemoresistance in glioblastoma multiforme (GBM), targeting GSCs is an attractive strategy to treat GBM. Utilizing an anti-cancer compound library, we identified R406, the active metabolite of a FDA-approved Syk inhibitor for immune thrombocytopenia (ITP), with remarkable cytotoxicity against GSCs but not normal neural stem cells. R406 significantly inhibited neurosphere formation and triggered apoptosis in GSCs. R406 induced a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS) and subsequently production of excess ROS in GSCs. R406 also diminished tumor growth and efficiently sensitized gliomas to temozolomide in GSC-initiating xenograft mouse models. Mechanistically, the anti-GSC effect of R406 was due to the disruption of Syk/PI3K signaling in Syk-positive GSCs and PI3K/Akt pathway in Syk-negative GSCs respectively. Overall, these findings not only identify R406 as a promising GSC-targeting agent but also reveal the important role of Syk and PI3K pathways in the regulation of energy metabolism in GSCs.

Topics: Animals; Antineoplastic Agents; Apoptosis; Brain Neoplasms; Cell Adhesion; Drug Resistance, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Glioblastoma; Glycolysis; Humans; Mice, Nude; Neoplastic Stem Cells; Oxazines; Oxidative Phosphorylation; Phosphatidylinositol 3-Kinases; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Pyridines; Signal Transduction; Survival Analysis; Syk Kinase; Temozolomide; Xenograft Model Antitumor Assays

2019