In contrast, U87-MG glioblastoma cells, which are much more dependent upon OXPHOS as a bioenergetic strategy [25], displayed clear changes in AMPK activation in response to the depletion of cellular ATP by mandelalide L. All compensatory survival signaling in these cells could be overwhelmed by prolonged exposure to mandelalide A, suggesting that the cytotoxic mandelalides are a potentially useful class of ATP synthase inhibitors to probe metabolic flexibility in glioblastoma cells and GSCs relative to astrocytes and other normal cell types. The gene discussed is PRKAA2; the disease is glioblastoma.