7ACC2 - CAS 1472624-85-3
Catalog number: 1472624-85-3
Category: Inhibitor
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7ACC2 did not influence the prothrombin time which, together with a good in vitro ADME profile, supports the potential of this new family of compounds to act as anticancer drugs through inhibition of lactate flux.
7ACC 2; 7ACC-2
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1.Interruption of lactate uptake by inhibiting mitochondrial pyruvate transport unravels direct antitumor and radiosensitizing effects.
Corbet C;Bastien E;Draoui N;Doix B;Mignion L;Jordan BF;Marchand A;Vanherck JC;Chaltin P;Schakman O;Becker HM;Riant O;Feron O Nat Commun. 2018 Mar 23;9(1):1208. doi: 10.1038/s41467-018-03525-0.
Lactate exchange between glycolytic and oxidative cancer cells is proposed to optimize tumor growth. Blocking lactate uptake through monocarboxylate transporter 1 (MCT1) represents an attractive therapeutic strategy but may stimulate glucose consumption by oxidative cancer cells. We report here that inhibition of mitochondrial pyruvate carrier (MPC) activity fulfils the tasks of blocking lactate use while preventing glucose oxidative metabolism. Using in vitro ;13;C-glucose and in vivo hyperpolarized ;13;C-pyruvate, we identify 7ACC2 as a potent inhibitor of mitochondrial pyruvate transport which consecutively blocks extracellular lactate uptake by promoting intracellular pyruvate accumulation. Also, while in spheroids MCT1 inhibition leads to cytostatic effects, MPC activity inhibition induces cytotoxic effects together with glycolysis stimulation and uncompensated inhibition of mitochondrial respiration. Hypoxia reduction obtained with 7ACC2 is further shown to sensitize tumor xenografts to radiotherapy. This study positions MPC as a control point for lactate metabolism and expands on the anticancer potential of MPC inhibition.
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CAS 1472624-85-3 7ACC2

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