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Small Molecule SGK Inhibitor Decreases Glioblastoma Cell Growth


Glioblastoma is the most common of all tumors in the brain and central nervous system and has an average survival time of less than one year. The current standard of care treats these tumors with radiation and temozolomide, a DNA alkylating agent, but a vast majority of these tumors have begun to acquire temozolomide resistance, highlighting the need for new therapies. The heterogeneous nature of glioblastoma tumors as well as the difficulty of drugs to cross the blood-brain barrier leads to minimal treatment options. To test potential small molecule inhibitors as treatment for glioblastoma, we exposed glioblastoma cells to four commercially available SGK (serum and glucocorticoid-regulated kinase) inhibitors, which target downstream effectors in the PI3K/Akt pathway regulating cell survival and proliferation. We found that one of the four SGK inhibitors, GSK650394, actively inhibits glioblastoma cell viability in U87MG and selectively target SGK at concentrations below 100 μM. This inhibitor could potentially be used to treat glioblastoma but must be further tested in heterogenous glioblastoma tumors and in vivo models, especially to study if these small molecule inhibitors can cross the blood-brain barrier, and the mechanism of action in glioblastoma must be further elucidated.

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