Carboxyamidotriazole inhibits oxidative phosphorylation in cancer cells and exerts synergistic anti-cancer effect with glycolysis inhibition.

•CAI is confirmed to inhibit OXPHOS in cancer cells for the first time.•Anti-cancer effect of CAI is greatly improved by being combined with 2-DG.•ATP decrease and G2/M arrest are caused by the combination of CAI and 2-DG.•Combination of CAI and 2-DG is well-tolerated and effective in a xenograft model.•Combination of CAI and 2-DG may potentiate other metabolism targeting approaches.