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 inhibits ASCT2-mediated glutamine uptake in human cells in a concentration-dependent fashion and exhibits a 100-fold improvement in potency over gamma-L-glutamyl-p-nitroanilide[1]. Pharmacological blockade of ASCT2 with V-9302 hydrochloride results in attenuated cancer cell growth and proliferation, increases cell death, and increases oxidative stress[1].

V-9302 hydrochloride (75 mg/kg; i.p.; daily fo 21 days) prevents tumor growth in both HCT-116 and HT29 xenograft models[1]. The combination of CB-839 and V-9302 (30 mg/kg; i.p.; SNU398 and MHCC97H cells were grown as tumor xenografts in BALB/c nude mice; for 20 or 15 d, respectively) elicits a strong growth inhibition in both SNU398 and MHCC97H xenograft models, while single-drug treatment showed modest anti-tumor effects[2]. V-9302 (50 mg/kg ; i.p.; daily for 5 days) displays markedly reduced tumor growth[3]. Animal Model: 6-week old, female athymic nude mice (bearing HCT-116 (KRASG13D) or HT29 (BRAFV600E) cell-line )[1]Dosage: 75 mg/kg Administration: Intraperitoneally; daily fo 21 days Result: Prevented tumor growth.