Fig. 5.

ONC201 and ONC206 target DMG bioenergetics, and combination of imipridones with glycolysis suppression potently inhibits tumor cell metabolism. (A and B) Mitochondrial respiration function, measured through oxygen consumption rate (OCR), was significantly (P < .0001) decreased after ONC201 and ONC206 treatment (IC₅₀) as single and combination agents. Arrows indicate addition of oligomycin (1), FCCP (2) and Rotenone/ AA (3). (C) Glycolysis, as measured by extracellular acidification rate (ECAR), was significantly reduced by ONC201 and combination treatment, whereas ONC206 showed a slight increase (IC₅₀). 2-deoxyglucose (2-DG) reduced glycolysis in all conditions. For (A-C): OCR/ECAR were measured 4 times with 5 replicates for each condition.