V-9302

V-9302 is a competitive antagonist of transmembrane glutamine flux. V-9302 selectively and potently targets the amino acid transporter ASCT2 (SLC1A5) not ASCT1. V-9302 inhibits ASCT2-mediated glutamine uptake (IC₅₀=9.6 µM) in HEK-293 cells^[1]. IC50 & Target:ASCT2^[1] In Vitro: V-9302 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 results in attenuated cancer cell growth and proliferation, increases cell death, and increases oxidative stress^[1]. In Vivo: V-9302 (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].