ASCT2-IN-1 (compound 20k) is an inhibitor of ASCT2, demonstrating IC50 values of 5.6 μM in A549 cells and 3.5 μM in HEK293 cells. It induces apoptosis and inhibits tumor growth.

ASCT2 (human):3.5 μM

ASCT2-IN-1 is a compound that, at a concentration of 50 μM for 15 minutes, inhibits Gln uptake in A549 and HEK293 cells by targeting hASCT, with IC50 values of 5.6 μM and 3.5 μM, respectively. At concentrations ranging from 0-50 μM over 15 minutes, it enhances metabolic stability in mouse liver microsomes, exhibiting a half-life of 37.15 minutes and a clearance rate of 37.48 μL/min•mg. ASCT2-IN-1 also inhibits the amino acid transporter SNAT2 in A549 cells and the LAT1 transporter in overexpressed HEK293 cells. In A549 cells, concentrations of 5-10 μM over 24 hours suppress Gln metabolism, increase ROS production, and induce apoptosis. Under starvation, this compound inhibits AKT phosphorylation and mTORC1 activity, promoting autophagy. Additionally, ASCT2-IN-1 inhibits the proliferation of A549 cells in a dose-dependent manner. It also suppresses organoid proliferation in NSCLCs, specifically in H1975 OR and HCC827 OR cells, at concentrations between 0-10 nM over 96 hours.

ASCT2-IN-2, when administered intraperitoneally at doses of 25 or 50 mg/kg every other day for three weeks, inhibits tumor growth by 65% in a BALB/c mouse NSCLC xenograft model.