7ACC2

7ACC2 is a carboxycoumarin inhibitor of monocarboxylate transporter 1 (MCT1) with an IC₅₀ value of 10 nM for lactate uptake, an MCT1-dependent process, in SiHa human cervix carcinoma cells.¹ It inhibits proliferation of SiHa cells in the presence of lactate in a dose-dependent manner but lacks cytotoxicity in the presence of glucose. 7ACC2 also inhibits the mitochondrial pyruvate carrier (MPC) in a concentration- and time-dependent manner in isolated tumor cell mitochondria.² In vivo, 7ACC2 (3 mg/kg) increases intratumor lactate accumulation and decreases tumor size in an SiHa mouse xenograft model.

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1. Draoui, N., Schicke, O., Fernandes, A., et al. Synthesis and pharmacological evaluation of carboxycoumarins as a new antitumor treatment targeting lactate transport in cancer cells. Bioorg. Med. Chem. 21(22), 7107-7117 (2013).

2. Corbet, C., Bastien, E., Draoui, N., et al. Interruption of lactate uptake by inhibiting mitochondrial pyruvate transport unravels direct antitumor and radiosensitizing effects. Nat. Commun. 9(1), 1208 (2018).