| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
The primary target of BSO is γ-glutamylcysteine synthetase (γ-GCS), the rate-limiting enzyme in the glutathione biosynthesis pathway. This enzyme catalyzes the condensation of glutamate and cysteine to form γ-glutamylcysteine, the first and rate-determining step in GSH synthesis. BSO acts as an irreversible inhibitor of this enzyme by binding competitively to the glutamate-binding site at the enzyme's active center, forming a stable enzyme-inhibitor complex and irreversibly blocking de novo GSH synthesis. Since GSH is the most abundant intracellular antioxidant, its depletion significantly enhances cellular sensitivity to oxidative stress and certain chemotherapeutic agents.
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| ln Vitro |
Buthionine suLfoximine is a methionine suLfoximine analogue that exhibits at least 100 times the efficiency of methionine suLfoximine in inhibiting γ-glutamylcysteine synthetase, compared to around 20 times that of methionine suLfoximine [1].
BSO exhibits selective cytotoxic activity against various tumor cell lines in vitro, with particular potency against malignant melanoma cells. Studies have shown that BSO has an IC₅₀ of 1.9 μM against melanoma cells, significantly lower than against breast cancer cells (8.6 μM) and ovarian cancer cells (29 μM). The sensitivity of melanoma cells correlates positively with their melanin content (r = 0.63). Mechanistically, treatment with 50 μM BSO for 48 hours results in a 95% decrease in GSH levels in melanoma cell lines, a 60% decrease in glutathione S-transferase (GST) enzyme activity, and significant downregulation of GST-μ protein and mRNA levels. Additionally, BSO augments lipopolysaccharide (LPS)-induced biosynthesis of the pro-inflammatory cytokines TNF-α and IL-6, an effect associated with the accumulation of reactive oxygen species (ROS). |
| ln Vivo |
A continuous intravenous infusion of non-toxic dosages of D,L-buthionine-(S,R)-imine (300 and 600 mg/kg/day) was administered to mice containing HT1080 and HT1080/DR4 xenografts. GSH tumor levels are decreased by more than 95% in multidrug additions and commonly decrease by 60% in parent cancers [2].
BSO demonstrates both single-agent anti-tumor activity and chemosensitizing effects in in vivo animal models. In melanoma xenograft models, BSO selectively inhibits tumor growth through mechanisms involving GSH depletion and GST downregulation. More importantly, BSO synergistically enhances the anti-tumor activity of alkylating agents such as carmustine (BCNU) against melanoma cell lines and human tumors. In preclinical studies, BSO reverses tumor cell resistance to platinum-based drugs and alkylating agents by depleting intracellular GSH, providing a rationale for combination chemotherapy strategies. |
| Enzyme Assay |
The inhibitory activity of BSO against γ-glutamylcysteine synthetase (γ-GCS) can be assessed using enzyme-coupled colorimetric assays. γ-GCS enzyme is extracted from rat liver or target cells. Various concentrations of BSO (0-1000 μM) are pre-incubated with the enzyme in reaction buffer (50 mM Tris-HCl, pH 8.2, containing 20 mM MgCl₂) with glutamate, cysteine, and ATP at 37°C for 15-30 minutes to allow irreversible binding of BSO to the enzyme. After substrate addition to initiate the reaction, the rate of absorbance decrease at 340 nm is monitored using an NADH oxidation coupling system to calculate the enzyme activity inhibition rate. The inhibition type (competitive/irreversible) and Ki value are analyzed by Lineweaver-Burk double reciprocal plots.
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| Cell Assay |
Exponentially growing tumor cells (e.g., melanoma M14, ZAZ cells, or human alveolar epithelial A549 cells) are seeded into 96-well culture plates at densities of 5×10³-1×10⁴ cells/well in medium containing 10% fetal bovine serum and cultured overnight. The following day, various concentrations of BSO (0-500 μM) are added and incubated for 24-72 hours. Cell viability is assessed using MTT or CCK-8 assays, with absorbance measured at 570 nm or 450 nm using a microplate reader. For mechanistic studies, total glutathione levels can be determined using the DTNB method, GST and γ-GCS protein expression can be detected by Western blot, and GST-μ mRNA levels can be measured by qRT-PCR. Cellular ROS levels can be detected using the DCFH-DA fluorescent probe by flow cytometry.
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| Animal Protocol |
Six-to-eight-week-old female nude mice are subcutaneously inoculated with melanoma cells (5×10⁶ cells/100 μL PBS) or other human tumor cell lines to establish xenograft models. When tumor volumes reach approximately 100-150 mm³, animals are randomly assigned to treatment groups (6-10 mice per group). BSO is prepared in saline and administered via intraperitoneal injection at typical doses of 5-10 mmol/kg (approximately 1.1-2.2 g/kg) once daily for 2-4 consecutive weeks. For combination therapy experiments, chemotherapeutic agents (e.g., melphalan or carmustine) are administered at specific time points after BSO administration (e.g., 4-6 hours, when GSH levels are maximally depleted). Tumor volume (length × width²/2) and body weight are measured 2-3 times weekly. At the end of the experiment, animals are euthanized, and tumor tissues are collected for GSH content and GST activity assays.
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| ADME/Pharmacokinetics |
The pharmacokinetics of BSO have been characterized in Phase I clinical trials in cancer patients. BSO consists of an equal mixture of R and S diastereoisomers, which exhibit stereoselective pharmacokinetic properties in vivo. S-BSO is the active isomer, while R-BSO is essentially inactive. The steady-state volume of distribution and renal clearance are similar for both isomers, but R-BSO exhibits higher total clearance and a shorter half-life, with approximately 25% faster elimination compared to S-BSO (p < 0.05). Renal clearance for both isomers approximates the glomerular filtration rate, accounting for 64% of total S-BSO clearance and 56% of total R-BSO clearance. Over the dose range of 5-10.5 g/m², the area under the concentration-time curve (AUC) is linearly related to dose for both isomers (R-BSO r² = 0.798; S-BSO r² = 0.752), indicating linear pharmacokinetics in this dose range. BSO concentrations in human plasma and urine can be quantified using reversed-phase HPLC or capillary electrophoresis methods.
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| Toxicity/Toxicokinetics |
The toxicological profile of BSO has been evaluated in animal studies and clinical trials. In animal studies, acute intraperitoneal administration of BSO in rats causes lung changes, liver effects, and maternal reproductive toxicity. In guinea pigs, two weeks of intermittent subcutaneous injection induces diffuse hepatitis. BSO is a strong irritant to skin and eyes. In clinical studies, the adverse effects of BSO in combination with melphalan primarily include predictable hematologic toxicities. Notably, the effective GSH-depleting concentration (achieving an IC₉₀ of 25.5 μM for melanoma) is 20-fold lower than steady-state plasma concentrations achievable clinically, suggesting a favorable therapeutic window for BSO. BSO powder can be stored at -20°C for 3 years, and in solution at -20°C for 6 months.
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| References |
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| Additional Infomation |
S-Butyl-DL-homocysteine (S,R)-sulfonylimine is a sulfonylimine derivative of a DL-methionine analog, wherein the S-methyl group is replaced by an S-butyl group. It is an EC 6.3.2.2 (glutamate-cysteine ligase) inhibitor and an inducer of ferroptosis. It comprises D-butyrosine-(S,R)-sulfonylimine and L-butyrosine-(S,R)-sulfonylimine. Butyrosine sulfonylimine has been used in research trials for the treatment of neuroblastoma and melanoma (skin). Butyrosine sulfonylimine is a synthetic amino acid. Butyrosine sulfonylimine irreversibly inhibits γ-glutamylcysteine synthase, thereby depleting intracellular glutathione. Glutathione is a metabolite that plays a crucial role in protecting cells from oxidative stress damage; its inhibition leads to free radical-induced apoptosis. Elevated glutathione levels are associated with resistance in tumor cells to alkylating agents and platinum compounds. By depleting intracellular glutathione, this drug may enhance the in vitro and in vivo cytotoxicity of various chemotherapeutic agents in drug-resistant tumors. Butylthionine sulfoxide imide may also possess anti-angiogenic activity. (NCI04)
A synthetic amino acid that depletes glutathione by irreversibly inhibiting γ-glutamylcysteine synthase. Inhibition of this enzyme is a key step in glutathione biosynthesis. Studies have shown that butylthionine sulfoxide imide can inhibit the proliferative response of human T lymphocytes and suppress macrophage activation. (J Biol Chem 1995;270(33):1945-7) |
| Molecular Formula |
C8H18N2O3S
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|---|---|
| Molecular Weight |
222.303
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| Exact Mass |
222.104
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| Elemental Analysis |
C, 43.22; H, 8.16; N, 12.60; O, 21.59; S, 14.42
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| CAS # |
5072-26-4
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| Related CAS # |
L-Buthionine-(S,R)-sulfoximine;83730-53-4;DL-Buthionine-(S,R)-sulfoximine hydrochloride;L-Buthionine-(S,R)-sulfoximine hydrochloride; 5072-26-4 (DL)
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| PubChem CID |
21157
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| Appearance |
White to off-white solid powder
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| Density |
1.29g/cm3
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| Boiling Point |
382.3ºC at 760 mmHg
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| Melting Point |
215ºC (dec.)(lit.)
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| Flash Point |
185ºC
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| Index of Refraction |
1.537
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| LogP |
2.301
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
14
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| Complexity |
284
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCS(=N)(=O)CCC(C(=O)O)N
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| InChi Key |
KJQFBVYMGADDTQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C8H18N2O3S/c1-2-3-5-14(10,13)6-4-7(9)8(11)12/h7,10H,2-6,9H2,1H3,(H,11,12)
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| Chemical Name |
2-amino-4-(butylsulfonimidoyl)butanoic acid
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| Synonyms |
Buthionine Sulphoximine; BSO; NSC326231;2-Amino-4-(S-butylsulfonimidoyl)butanoic acid; CHEBI:176510; RefChem:1062180; 5072-26-4; BUTHIONINE SULFOXIMINE; NSC-326231
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ~25 mg/mL (~112.46 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (449.82 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.4984 mL | 22.4921 mL | 44.9843 mL | |
| 5 mM | 0.8997 mL | 4.4984 mL | 8.9969 mL | |
| 10 mM | 0.4498 mL | 2.2492 mL | 4.4984 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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