NAMPT inhibition impairs cellular respiration in AML cells. (A) Oxygen consumption rate (OCR) measured before and after the addition of the inhibitors oligomycin, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), and rotenone to derive several parameters of mitochondrial respiration following KPT-9274 treatment (24 hours, 250 nM; n = 3). (B) Results of glycolytic stress testing using MV4-11 and THP-1 cell lines (24 hours, 250 nM; n = 3). (C) Mitochondrial activity of patient samples treated with venetoclax given in combination with different doses of KPT-9274 in the presence of stromal protection (n = 5; error bars were removed for clarity). (D) Analysis of synergistic effect of combination of KPT-9274 with venetoclax, showing significant synergy at the 100-nM dose of KPT-9274 in combination with the 10-nM dose of venetoclax using Combenefit software analysis. ECAR, extracellular acidification rate.