ASCT2-IN-2

ASCT2-IN-2 (compound 25e) is an ASCT2 inhibitor with IC50 of 5.14 μM. ASCT2-IN-2 regulates amino acid metabolism as well as mTOR signaling and thereby induces cell apoptosis. ASCT2-IN-2 inhibits tumor growth.

ASCT2-IN-2 (50 μM, 15 min) inhibits Glutamine (Gln) uptake in cells A549 and HEK293 (Gln inhibition ratio 55.62% and 98.31%) by targeting hASCT2, with IC50 values of 5.6 μM and 3.5 μM, respectively[1]. ASCT2-IN-2 (0-50 μM, 15 min) improves metabolic stability in murine liver microsome, with a half-time of 166.51 min and a clearance of 8.27 μL/min•mg[1].ASCT2-IN-2 (0-50 μM, 15 min) improves activity of LAT1 and thereby promotes leucine uptake in A549 cells[1].ASCT2-IN-2 (5-10 μM, 24 h) inhibits Gln metabolism, upregulates the ROS production and thereby induces apoptosis in cell A549[1].ASCT2-IN-2 (5-10 μM, 24 h) inhibits AKT phosphorylation and mTORC1 activity under starvation, promotes cell autophagy[1].ASCT2-IN-2 (5-10 μM, 24 h) dose-dependently inhibits proliferation in A549[1].ASCT2-IN-2 (0-10 nM, 96 h) inhibits organoid proliferation of drug resistant NSCLCs in cells H1975 OR and HCC827 OR [1].

ASCT2-IN-2 (i.p.;25 or 50 mg/kg, once every two days for 3 weeks) inhibits tumor growth with a TGI of 70% in A549 Xenograft Model in BALB/c mice[1].Pharmacokinetic Analysis of ASCT2-IN-2 in Sprague-Dawley rats[1]

References:
[1]. Qin L et al., Discovery of Novel Aminobutanoic Acid-Based ASCT2 Inhibitors for the Treatment of Non-Small-Cell Lung Cancer. J Med Chem. 2024 Jan 13. doi: 10.1021/acs.jmedchem.3c01093