Buthionine Sulfoximine

Buthionine Sulfoximine (CAS No.: 83730-53-4) is a cell-permeable, potent, and irreversible inhibitor of γ-glutamylcysteine synthetase, the rate-limiting enzyme in glutathione biosynthesis, and is widely used as a biochemical tool to deplete intracellular glutathione and modulate cellular redox homeostasis. By suppressing glutathione production, it induces oxidative stress, elevates reactive oxygen species levels, and disrupts antioxidant defense systems, thereby influencing multiple signaling pathways associated with cell survival, proliferation, and programmed cell death. In vitro studies demonstrate that Buthionine Sulfoximine inhibits the growth of various cancer cell types, including melanoma, breast, ovarian, and glioblastoma cells, with activity observed in the low micromolar to tens of micromolar range, and can promote ferroptosis or apoptosis depending on cellular context and combination treatments. It also significantly reduces glutathione and cysteine levels, decreases glutathione S-transferase activity and expression, and increases DNA damage and deletion frequency, highlighting its role in genomic instability under oxidative stress conditions. In animal models, systemic administration has been shown to lower fetal and tissue glutathione levels and increase biomarkers of DNA damage. As a result, Buthionine Sulfoximine is extensively employed in cancer biology, redox regulation studies, and drug sensitization research, particularly for investigating mechanisms of oxidative stress–mediated cytotoxicity and enhancing the efficacy of chemotherapeutic or pro-oxidant agents, with experimental concentrations or dosing regimens varying according to specific study designs.