In the last few years, several efforts have been ended to identify original strategies against gli-oblastoma multiforme (GBM): this requires a more detailed investigation of the molecular mechanism of GBM so that novel targets can be identified for new possible therapeutic agents. Here, using a combined proteomic approach, we evaluated the ability of a blood brain barrier permeable 2,3-benzodiazepin-4-one, called 1g, to interfere with the activity and the expression of brain glycogen phosphorylase (PYGB) on U87MG cell line in parallel with the capability of this compound to inhibit the cell growth and cycle. Thus, our results highlighted PYGB as a potential metabolic target in GBM prompting 1g as a capable anticancer drug thanks to its ability to nega-tively modulate the uptake and metabolism of glucose, the so called “Warburg effect”, whose increase is considered a common feature of cancer cells in respect of their normal counterparts.