L-Buthionine-(S,R)-sulfoximine (L-Butionine sulfoximine)
(Synonyms: 丁硫氨酸-亚砜亚胺,L-BSO) 目录号 : GC33098
An irreversible inhibitor of the γ-glutamylcysteine synthetase
Cas No.:83730-53-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Animal experiment: |
Mice[2]C57BL/6J pun/pun mice are used in the study. Pregnancy is timed by checking for vaginal plugs. Noon of the day of discovery is counted as 0.5 days post coitum (d.p.c.). Similarly, the time of birth of a litter is timed with the noon of discovery counted as 0.5 days post-partum (d.p.p.). Pregnant dams are given free access to drinking water supplemented by either 2 mM L-Buthionine-(S,R)-sulfoximine (BSO), 20 mM BSO, 2 mM BSO and 20 mM NAC, 20 mM NAC or unsupplemented water for 18 days from 0.5 to 18.5 d.p.c. The pH of supplemented water is as follows: 6.88, 20 mM BSO; 3.37, 2 mM BSO; 2.65, 2 mM BSO plus 20 mM NAC; and 2.58, 20 mM NAC. The pH of regular water used in our facility is ~4. To determine the DNA deletion frequency, 20-day-old offspring (23 mice in the control group and 16-17 mice per exposure group) are sacrificed to visualize eye-spots (DNA deletions) in their RPE[2]. |
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References: [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. |
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L-Buthionine-(S,R)-sulfoximine is an irreversible inhibitor of γ-glutamylcysteine synthetase (Ki = 25 ?M).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 ?M, respectively).2 L-Buthionine-(S,R)-sulfoximine (100?M) 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 ?M. 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.
L-丝氧化-双硫仑是γ-谷氨酰半胱氨酸合成酶的不可逆抑制剂（Ki = 25μM）。1它抑制了ZAZ和M14黑色素瘤细胞、A2780卵巢和MCF-7乳腺癌细胞的增殖（分别的IC50为4.9、18、8.5和26.5μM）。2 L-丝氧化-双硫仑（100μM）会诱导A172和T98G胶质母细胞瘤细胞发生铁死亡。3在浓度为10μM时，它会增加HeLa细胞内活性氧（ROS）的水平。L-丝氧化-双硫仑（1mM）与甲基乙酰中毒结合时，可以诱导牛主动脉内皮细胞（BAECs）凋亡。4当孕母以2和20mM的浓度在饮用水中摄入时，它会增加小鼠幼仔视网膜色素上皮中的眼斑数量，这是DNA缺失的指标。5当孕母摄入时，L-丝氧化-双硫仑会降低胎儿小鼠中的半胱氨酸和谷胱甘肽（GSH）水平。
1.Griffith, O.W.Mechanism of action, metabolism, and toxicity of buthionine sulfoximine and its higher homologs, potent inhibitors of glutathione synthesisJ. Biol. Chem.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-transferasePigment 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 ferroptosisJ. Biol. Chem.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 cellsBiol. Pharm. Bull.33(4)556-560(2010) 5.Reliene, R., and Schiestl, R.H.Glutathione depletion by buthionine sulfoximine induces DNA deletions in miceCarcinogenesis27(2)240-244(2006)
| Cas No. | 83730-53-4 | SDF | |
| 别名 | 丁硫氨酸-亚砜亚胺,L-BSO | ||
| Canonical SMILES | N[C@H](C(O)=O)CCS(CCCC)(=O)=N | ||
| 分子式 | C8H18N2O3S | 分子量 | 222.31 |
| 溶解度 | Water : 41.67 mg/mL (187.44 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.4982 mL | 22.4911 mL | 44.9822 mL |
| 5 mM | 0.8996 mL | 4.4982 mL | 8.9964 mL |
| 10 mM | 0.4498 mL | 2.2491 mL | 4.4982 mL |
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每只动物给药体积 | ul | |
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Cytotoxicity of antitumor platinum complexes with L-buthionine-(R,S)-sulfoximine and/or etanidazole in human carcinoma cell lines sensitive and resistant to cisplatin
Cancer Chemother Pharmacol 1995;36(5):431-8.PMID:7634385DOI:10.1007/BF00686193.
Human 2008 ovarian carcinoma cells and the C13 CDDP-resistant subline and human MCF-7 breast carcinoma cells and the MCF-7/CDDP CDDP-resistant subline were exposed to L-Buthionine-\(S,R\)-sulfoximine (50 microM) for 48 h prior to and during exposure for 1 h to the antitumor platinum complexes, cis-diamminedichloroplatinum(II), carboplatin or D,L-tetraplatin and/or to etanidazole (1 mM) for 2 h prior to and during exposure for 1 to the antitumor platinum complexes. These modulators alone did not significantly alter the cytotoxicity of CDDP toward either parental line. A twofold enhancement in cytotoxicity was observed with carboplatin in the 2008 cells and with D,L-tetraplatin in both parental lines with the single modulators. The modulator combination (buthionine sulfoximine/etanidazole) was very effective along with D,L-tetraplatin in both the MCF-7 parent and MCF-7/CDDP cell lines where at the higher platinum complex concentrations there was 1.5 to 3 logs increased killing of cells by the drug plus the modulators compared with the drug alone. Similarly, when C13 cells were exposed to CDDP (100 microM) or D,L-tetraplatin (100 microM) along with buthionine sulfoximine and etanidazole there was a 2-log increase in cell killing compared with exposure to the platinum complex alone. Treatment of each of the four cell lines with buthionine sulfoximine decreased both the non-protein and total sulfhydryl content of the cells. Treatment with the combination of modulators did not produce a further decrease in cellular sulfhydryl content compared with buthionine sulfoximine alone. The total sulfhydryl content in MCF-7 cells and 2008 cells exposed to buthionine sulfoximine and etanidazole was 58% and 31% of normal and the total sulfhydryl content of MCF-7/CDDP cells and C13 cells treated the same way was 54% and 23% of normal, respectively. DNA alkaline elution was used to assess the impact of exposure to the modulators, buthionine sulfoximine and etanidazole, alone and in combination on the cross linking of DNA by the antitumor platinum complexes in the MCF-7 and MCF-7/CDDP cell lines. Overall, the increases in DNA cross linking factors were greater in the MCF-7 cells than in the MCF-7/CDDP cells. These results indicate a possible clinical potential for this modulator combination.
Determination of L-Buthionine-\(S,R\)-sulfoximine in plasma by high-performance liquid chromatography with o-phthalaldehyde derivatization and fluorometric detection
J Chromatogr 1987 Jan 9;385:275-82.PMID:3558582DOI:10.1016/s0021-9673(01)94640-0.
The development of a high-performance liquid chromatography system for the analysis of L-Buthionine-\(S,R\)-sulfoximine (BSO) in human plasma is described. o-Phthalaldehyde derivatization and fluorescence detection were used. The R- and S-BSO peaks were partially separated from each other and completely separated from the matrix components. The limit of detection for BSO was 2 micrograms/ml plasma.
In vivo inhibition of l-buthionine-(S,R)-sulfoximine-induced cataracts by a novel antioxidant, N-acetylcysteine amide
Free Radic Biol Med 2011 Mar 15;50(6):722-9.PMID:21172425DOI:10.1016/j.freeradbiomed.2010.12.017.
The effects of N-acetylcysteine amide (NACA), a free radical scavenger, on cataract development were evaluated in Wistar rat pups. Cataract formation was induced in these animals with an intraperitoneal injection of a glutathione (GSH) synthesis inhibitor, L-Buthionine-\(S,R\)-sulfoximine (BSO). To assess whether NACA has a significant impact on BSO-induced cataracts, the rats were divided into four groups: (1) control, (2) BSO only, (3) NACA only, and (4) NACA+BSO. The control group received only saline ip injections on postpartum day 3, the BSO-only group was given ip injections of BSO (4mmol/kg body wt), the NACA-only group received ip injections of only NACA (250mg/kg body wt), and the NACA+BSO group was given a dose of NACA 30min before administration of the BSO injection. The pups were sacrificed on postpartum day 15, after examination under a slit-lamp microscope. Their lenses were analyzed for selective oxidative stress parameters, including glutathione (reduced and oxidized), protein carbonyls, catalase, glutathione peroxidase, glutathione reductase, and malondialdehyde. The lenses of pups in both the control and the NACA-only groups were clear, whereas all pups within the BSO-only group developed well-defined cataracts. It was found that supplemental NACA injections during BSO treatment prevented cataract formation in most of the rat pups in the NACA+BSO group. Only 20% of these pups developed cataracts, and the rest retained clear lenses. Further, GSH levels were significantly decreased in the BSO-only treated group, but rats that received NACA injections during BSO treatment had these levels of GSH replenished. Our findings indicate that NACA inhibits cataract formation by limiting protein carbonylation, lipid peroxidation, and redox system components, as well as replenishing antioxidant enzymes.
Oxidative stress induced by L-Buthionine-\(S,R\)-sulfoximine, a selective inhibitor of glutathione metabolism, abrogates mouse kidney mineralocorticoid receptor function
Biochim Biophys Acta 2000 Feb 28;1495(3):263-80.PMID:10699465DOI:10.1016/s0167-4889(99)00166-4.
In vitro studies have demonstrated that cysteine groups present in most of the steroid receptors play an essential role in the steroid binding process as well as in the ability of this superfamily of signaling proteins to function as transcription factors. However, there is poor experimental evidence, if any, which demonstrates that under conditions of oxidative stress the steroid receptors in general, and the mineralocorticoid receptor in particular, are affected in vivo in a similar fashion as has been described for cell-free systems or cells in culture. In the present work we report that when mice are exposed to oxidative stress by treatment with L-Buthionine-\(S,R\)-sulfoximine (L-(S,R)-BSO), a glutathione depleting agent, the aldosterone-dependent mineralocorticoid biological response (measured as sodium retention and potassium elimination) was diminished in a directly proportional manner with respect to the depletion of renal glutathione. Accordingly, the steroid binding capacity of the mineralocorticoid receptor was also abrogated, whereas the receptor protein level remained unchanged. The harmful effects observed in mice after glutathione depletion were efficiently prevented by co-treatment with glutathione monoethyl ester. Similar inhibition in the steroid binding capacity was also generated in vitro by receptor alkylation and receptor oxidation, an effect which was prevented in the presence of reducing agents. Since the glutathione deficit generated in vivo by treatment with L-(S,R)-BSO did not significantly affect other renal proteins which are known to be required for the mineralocorticoid mechanism of action, we suggest that in renal cells a low redox potential exerts drastic and uncompensated inhibition of the receptor-mediated mineralocorticoid biological response. This effect was ascribed to the loss of steroid binding capacity of oxidized receptor, most likely by modification of essential cysteines as supported by experiments where a decreased number of reactive thiols and reduced covalent binding of thiol-reactive ligand were evidenced on immunopurified receptor after in vivo treatment with L-(S,R)-BSO.
d,L-Buthionine-\(S,R\)-sulfoximine potentiates in vivo the therapeutic efficacy of doxorubicin against multidrug resistance protein-expressing tumors
Clin Cancer Res 1996 Dec;2(12):1961-8.PMID:9816155doi
Intracellular glutathione (GSH) has been implicated as a regulatory determinant of multidrug resistance protein (MRP) function. The objective of the present study was to evaluate in vivo the ability of d,L-Buthionine-\(S,R\)-sulfoximine (d,l-BSO), a potent inhibitor of GSH biosynthesis, to reverse MRP-mediated drug resistance to doxorubicin. Athymic nude mice (nu/nu) bearing advanced parental human fibrosarcoma HT1080 and MRP-expressing HT1080/DR4 tumors were treated with the maximum tolerated dose of doxorubicin (10 mg/kg, i. v. push). This therapy produced an overall response rate of 50% (20% complete response and 30% partial response) in mice bearing parental HT1080 xenografts, whereas no significant antitumor activity against HT1080/DR4 tumors was observed. Treatment of mice bearing HT1080 and HT1080/DR4 xenografts with a continuous i.v. infusion of nontoxic doses of d,l-BSO (300 and 600 mg/kg/day) produced a 60% reduction of GSH plasma levels and greater than 95% reduction in GSH tumor levels in both parental and multidrug-resistant tumors; however, this treatment possessed no in vivo antitumor activity by itself. Under these treatment conditions, a combination of d,l-BSO with the maximum tolerated dose of doxorubicin administered at 24 h during a 48-h i.v. infusion of d,l-BSO completely restored the response of MRP-expressing HT1080/DR4 tumors to doxorubicin (overall response rate, 63%; complete response rate, 38%) with no potentiation of host toxicity. The d,l-BSO-induced in vivo reversal of MRP-mediated drug resistance correlated in vitro with the restoration of intracellular doxorubicin retention in cultured HT1080/DR4 cells. Depletion of GSH by d,l-BSO in drug-sensitive HT1080 tumors that do not express MRP did not alter the in vivo response to doxorubicin. Using the same treatment schedule, dose, and administration of doxorubicin with and without d,l-BSO in nude mice bearing P-170 glycoprotein-expressing A2780/Dx5 tumors, no potentiation of the therapeutic index of doxorubicin was found, demonstrating the in vivo selectivity of d, l-BSO-induced GSH depletion on MRP-function. The data reported herein indicate that in vivo function of MRP as a mediator of doxorubicin resistance requires the presence of sufficient GSH pools. d,l-BSO may provide an example of an effective in vivo modulator of MRP-mediated drug resistance.