L-Buthionine-(S,R)-sulfoximine hydrochloride 是一种具有细胞渗透性的、有效的、快速起效的、具有口服活性的、不可逆的 G-谷氨酸半胱氨酸合成酶 (γ-glutamylcysteine synthetase) 抑制剂，可降低细胞内谷胱甘肽的水平，其对黑色素瘤、乳腺卵巢癌标本的 IC50 值分别为1.9 μM、8.6 μM 和29 μM。
货号:ajcx34130
CAS:N/A
分子式:C8H19ClN2O3S
分子量：258.77
溶解度:DMSO : 250 mg/mL (966.11 mM; Need ultrasonic)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

L-Buthionine-(S,R)-sulfoximine hydrochloride is a cell-permeable, potent, fast acting, orally active and irreversible inhibitor of g-glutamylcysteine synthetase and depletes cellular glutathione levels. The IC50 value of L-Buthionine-(S,R)-sulfoximine on melanoma, breast and ovarian tumor specimens are 1.9 μM, 8.6 μM, and 29 μM, respectively[1][2].

L-Buthionine-(S,R)-sulfoximine (BSO: 50 μM) treatment for 48 hr results in a 95% decrease in ZAZ and M14 melanoma cell line GSH levels, and a 60% decrease in GST enzyme activity. GST-π protein and mRNA levels are significantly reduced in both cell lines[1]. L-Buthionine-(S,R)-sulfoximine (BSO) induces oxidative stress in a cell by irreversibly inhibiting g-glutamylcysteine synthetase, an essential enzyme for the synthesis of glutathione (GSH)[2].L-Buthionine-(S,R)-sulfoximine (BSO) induces ferroptosis in cancer cells[3].

BSO causes an elevated frequency of DNA deletions during mouse development. BSO treatment reduced GSH concentration in mouse fetuses by 55% and 70% at 2 mM and 20 mM BSO doses, respectively, compared to untreated mice. Co-treatment with 2 mM BSO and 20 mM NAC depleted GSH to a similar extent as 2 mM BSO, consistent with the function of BSO to inhibit the g-GCS enzyme indispensable for GSH synthesis. Like GSH, cysteine levels dropped following BSO treatment[2].

[1]. Fruehauf JP, 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. 1997 Aug;10(4):236-49.
[2]. Reliene R, et al. Glutathione depletion by buthionine sulfoximine induces DNA deletions in mice. Carcinogenesis. 2006 Feb;27(2):240-4.
[3]. Satoru Nishizawa, et al. Low tumor glutathione level as a sensitivity marker for glutamate-cysteine ligase inhibitors. Oncol Lett. 2018 Jun;15(6):8735-8743.