Biological Activity
7acc2, a carboxycoumarin derivative, is a potent inhibitor of monocarboxylate transporter 1 (mct1), with an ic50 value of ~ 10 nm for lactate uptake in the human cervix carcinoma cell line siha. the family of mct is composed of 14 members, among which only four isoforms (i.e. mct1-4) have been documented to act as proton-linked transporters carrying short chain monocarboxylates such as lactate and pyruvate across cell membranes. in cancer cells, mct1 and mct4 are the most widely expressed, and mct1 shows a better affinity for l-lactate than mct4, enabling lactate entry into oxidative tumor cells. thus, mct1 blockade could serve as a potential therapeutic strategy to limit cancer progression. in addition, 7acc2 is also a potent inhibitor of mitochondrial pyruvate transport, which interferes with pyruvate import into mitochondria and ultimately prevents extracellular lactate uptake as efficiently as a mct1 inhibitor.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. bioorganic & medicinal chemistry, 2013, 21(22): 7107-7117.2. corbet c, bastien e, draoui n, et al. interruption of lactate uptake by inhibiting mitochondrial pyruvate transport unravels direct antitumor and radiosensitizing effects. nature communications, 2018, 9(1): 1208.
