V-9302 | Glutamine transport inhibitor

V-9302 (1855871-76-9) is a selective inhibitor of the alanine-serine-cysteine transporter 2 (ASCT2 or SLC1A5; IC₅₀ = 9.0 µM rat and 9.6 µM human).^1,2  It inhibited the uptake of glutamine and possibly other amino acids in human cancer cells and reduced in vitro viability by at least 20% in more than half of 29 cancer cell lines screened.² V-9302 decreased mTOR activity, elevated autophagy, and increased oxidative stress in multiple animal cancer models.^2-5

References/Citations:

1. Schulte et al. (2016), 2-Amino-4-bis(aryloxybenzyl)aminobutanoic acids: a novel Scaffold for inhibition of ASCT2-mediated glutamine transport; Bioorg. Med. Chem. Lett., 26 1044
2. Schulte et al. (2018), Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models; Nat. Med., 24 194
3. Zhang (2020), ASCT2 (SLC1A5)-dependent glutamine uptake is involved in the progression of head and neck squamous cell carcinoma; Br. J. Cancer, 122 82
4. Jin et al. (2020), A powerful drug combination strategy targeting glutamine addiction for the treatment of human liver cancer; Elife, 9 e56749
5. Edwards et al. (2021), Selective glutamine metabolism inhibition in tumor cells improves antitumor T lymphocyte activity in triple-negative breast cancer; J. lin. Invest., 131 e140100