Abstract
The heterogeneous nature of glioblastoma has hampered the development of new effective therapeutic options. This heterogeneity is partially attributed to a subset of tumor cells known as brain tumor initiating cells (BTICs) that are highly tumorigenic and have some properties of neural stem cells. BTICs display metabolic plasticity, but, like many cancer cells, can have a reliance on aerobic glycolysis. Elevated expression of the glucose transporters GLUT1 and GLUT3 is present in many cancer types, with GLUT3 being preferentially expressed in BTICs to promote survival in low nutrient microenvironments. Through structure-based virtual screening, we identified potential novel GLUT inhibitors. The screening of 13 compounds identified two that can preferentially inhibit the growth of BTICs with minimal toxicity to non-neoplastic astrocytes and neurons. These compounds, SR37683 and SR37684, also inhibit glucose uptake and reduce glycolytic metabolism in Seahorse assays. We intend to identify a potential new therapeutic option targeting metabolic reprogramming for the treatment of glioblastoma, as well as other tumor types.