D,L-Buthionine-(S,R)-sulfoximine (Butionine sulfoximine)
(Synonyms: 丁基硫,Buthionine sulfoximine; BSO) 目录号 : GC33023
A γ-glutamylcysteine synthetase inhibitor
Cas No.:5072-26-4
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
|
Animal experiment: |
Mice[2]D,L-Buthionine-(S,R)-sulfoximine is dissolved in sterile 0.9% saline, filtered through a 0.2-p.m polysulfone membrane filter, and administered by 48-h continuous iv. infusion at a dose of 300 mg/kg/day and 600 mg/kg/day starting at 24 h before doxorubicin administration. In vivo GSH levels after treatment with D,L-Buthionine-(S,R)-sulfoximine at a dose of 300 mg/kg and 600 mg/kg for 24 h as an iv. continuous infusion in munine plasma and in tumor tissue of HT1080 and HT1080/DR4 xenografts is measured[2]. |
|
References: [1]. Griffith OW, et al. Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine). J Biol Chem. 1979 Aug 25;254(16):7558-60. |
|
D,L-Buthionine-(S,R)-sulfoximine is an inhibitor of γ-glutamylcysteine synthetase that induces 100% inhibition at a concentration of 10 μM in an enzyme assay.1 It is selective for γ-glutamylcysteine synthetase, lacking activity at glutamine synthetase at concentrations up to 500 μM. D,L-Buthionine-(S,R)-sulfoximine (32 mmol/kg, i.p.) reduces renal glutathione in mice without inducing abnormal behavior or convulsions. It has antiparasitic activity, eliminating T. brucei from the bloodstream of infected mice via depletion of intratrypanosomal glutathione and induction of oxidative stress at a dose of 4 mmol/kg.2 D,L-Buthionine-(S,R)-sulfoximine is an isomeric mixture of L-buthionine-S-sulfoxime, L-buthionine-R-sulfoxime, D-buthionine-S-sulfoxime, and D-buthionine-R-sulfoxime.
1.Griffith, O.W., and Meister, A.Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine)J. Biol. Chem.254(16)7558-7560(1979) 2.Arrick, B.A., Griffith, O.W., and Cerami, A.Inhibition of glutathione synthesis as a chemotherapeutic strategy for trypanosomiasisJ. Exp. Med.153(3)720-725(1981)
| Cas No. | 5072-26-4 | SDF | |
| 别名 | 丁基硫,Buthionine sulfoximine; BSO | ||
| Canonical SMILES | OC(C(N)CCS(CCCC)(=N)=O)=O | ||
| 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。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
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.