L-Buthionine-(S,R)-Sulfoximine

L-Buthionine-(S,R)-sulfoximine is an irreversible inhibitor of γ-glutamylcysteine synthetase (K_i = 25 µM).¹ It inhibits the proliferation of ZAZ and M14 melanoma cells, as well as A2780 ovarian and MCF-7 breast cancer cells (IC₅₀s = 4.9, 18, 8.5, and 26.5 µM, respectively).² L-Buthionine-(S,R)-sulfoximine (100µM) induces ferroptosis in A172 and T98G glioblastoma cells.³ It increases reactive oxygen species (ROS) levels in HeLa cells when used at a concentration of 10 µM. L-Buthionine-(S,R)-sulfoximine (1 mM), in combination with methylglyoxal, induces apoptosis of bovine aortic endothelial cells (BAECs).⁴ It increases the number of eye spots in the retinal pigment epithelium, an indicator of DNA deletions, in mouse pups when administered to pregnant dams at concentrations of 2 and 20 mM in the drinking water.⁵ L-Buthionine-(S,R)-sulfoximine decreases cysteine and glutathione (GSH) levels in fetal mice when administered to pregnant dams.

WARNING This product is not for human or veterinary use.

1. Griffith, O.W. Mechanism of action, metabolism, and toxicity of buthionine sulfoximine and its higher homologs, potent inhibitors of glutathione synthesis. The Journal of Biological Chemisty 257(22), 13704-13712 (1982).

2. Fruehauf, J.P., Zonis, S., al-Bassam, M., et al. Selective and synergistic activity of L-S,R-buthionine sulfoximine on malignant melanoma is accompanied by decreased expression of glutathione-S-transferase. Pigment Cell Res. 10(4), 236-249 (1997).

3. Hayashima, K., and Katoh, H. Expression of gamma-glutamyltransferase 1 in glioblastoma cells confers resistance to cystine deprivation-induced ferroptosis. The Journal of Biological Chemisty 298(3), 101703 (2022).

4. Takahashi, K., Tatsunami, R., Oba, T., et al. Buthionine sulfoximine promotes methylglyoxal-induced apoptotic cell death and oxidative stress in endothelial cells. Biol. Pharm. Bull. 33(4), 556-560 (2010).

5. Reliene, R., and Schiestl, R.H. Glutathione depletion by buthionine sulfoximine induces DNA deletions in mice. Carcinogenesis 27(2), 240-244 (2006).

Wang, X., Shelton, S.D., Bordieanu, B., et al. Scinderin promotes fusion of electron transport chain dysfunctional muscle stem cells with myofibers. Nat. Aging 2(2), s43587-43021-00164-x. (2024).

Kremer, D.M., Nelson, B.S., Lin, L., et al. GOT1 inhibition primes pancreatic cancer for ferroptosis through the autophagic release of labile iron. bioRxiv (2020).

Spangler, B., Morgan, C.W., Fontaine, S.D., et al. A reactivity-based probe of the intracellular labile ferrous iron pool. Nat. Chem. Biol. 12(9), 680-685 (2016).