PR002501 (Project)

Description:Amino acid uptake by the solute carrier family of transporter proteins is critical to support cell metabolism, and inhibition of transporter activity represents a tractable strategy to restrict nutrient availability to cancer cells. A small molecule inhibitor of the sodium-coupled neutral amino acid transporter 2 (SNAT2), 3-(N-methyl(4-methylphenyl)sulfonamido)-N-(2-trifluoromethylbenzyl)thiophene-2-carboxamide (MMTC/57E), was recently identified and was shown to inhibit cell proliferation when combined with glucose transport inhibitors in breast and pancreatic cancer cell lines. In this study, we use mass spectrometry-based metabolomics and establish cell-based assays for the SNAT2 transporter. We show that SNAT2 knockout cells have significant defects in amino acid availability. Using our established assays, we fail to observe that MMTC/57E inhibits SNAT2 activity likely due to its poor solubility.