7ACC2 is a potent MCT inhibitor with IC50 of 11 nM for inhibition of [14C]-lactate influx for antitumor treatment targeting lactate transport in cancer cells.
7ACC2, a potent monocarboxylate transporter (MCT) inhibitor with an IC50 of 11 nM for [14C]-lactate influx inhibition, also serves as a strong inhibitor of mitochondrial pyruvate transport. 7ACC2 is identified as an anticancer agent by impeding lactate flux[1][2].
体内研究
7ACC2 (compound 19) administered intraperitoneally at 3 mg/kg daily for 5 or 10 days significantly hinders tumor growth in mice, sensitizing tumor cells to radiation by reducing hypoxia[2].
The intraperitoneal injection of 7ACC2 (compound 19) at 3 mg/kg in mice rapidly achieves a peak concentration (Cmax) of 1246 ng/ml (4 μM) within 10 minutes (Tmax), with a plasma half-life of 4.5 hours[1].
体外研究
7ACC2 (compound 19) at 72 hours suppresses SiHa cell proliferation in a lactate-enriched medium with an EC50 of 0.22 μM, indicating lactate uptake is predominantly mediated by the high-affinity MCT1 transporter[1].
7ACC2 (compound 19) exhibits high chemical stability in simulated gastric (SGF) and intestinal (SIF) fluids, effective permeability through Caco-2 monolayers, and high metabolic stability in mouse (MLM) and human liver microsomes (HLM) as well as in human hepatocytes[1].
7ACC2 is a formidable inhibitor of mitochondrial pyruvate transport, effectively blocking extracellular lactate uptake and leading to an accumulation of intracellular pyruvate[2].
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