V-9302 hydrochloride is a potent and selective competitive antagonist that inhibits transmembrane glutamine flux by specifically targeting the amino acid transporter ASCT2 (SLC1A5), and not ASCT1. In HEK-293 cells, V-9302 hydrochloride effectively inhibits ASCT2-mediated glutamine uptake with an IC50 value of 9.6 μM.

V-9302 hydrochloride effectively hinders ASCT2-mediated glutamine absorption in human cells, displaying concentration-dependent activity and demonstrating a potency 100 times greater than that of gamma-L-glutamyl-p-nitroanilide[1]. The pharmacological inhibition of ASCT2 by V-9302 hydrochloride leads to reduced cancer cell growth and proliferation, heightened cell death, and augmented oxidative stress[1].

V-9302 hydrochloride, administered daily at a dosage of 75 mg/kg intraperitoneally (i.p.) for 21 days, effectively prevents tumor growth in HCT-116 and HT29 xenograft models. When combined with CB-839, V-9302 at 30 mg/kg enhances growth inhibition substantially in SNU398 and MHCC97H xenograft models, compared to modest anti-tumor effects observed with either drug alone. This combination treatment was applied for 20 or 15 days, respectively, in these models using SNU398 and MHCC97H cells implanted in BALB/c nude mice. Moreover, a once-daily administration of V-9302 (50 mg/kg; i.p.) for 5 days significantly reduces tumor growth. The studies used 6-week old, female, athymic nude mice bearing HCT-116 (KRASG13D) or HT29 (BRAFV600E) cell lines, showcasing V-9302's potential as a potent antitumor agent.