L-Buthionine-(S,R)-sulfoximine is a cell-penetrating/penetrable, potent, rapid-acting, irreversible inhibitor of G-glutamylcysteine synthetase (γ-glutamylcysteine synthetase). It can reduce intracellular glutathione levels, and its IC50s for melanoma and breast and ovarian cancer specimens are 1.9 μM, 8.6 μM and 29 μM respectively.

Physicochemical Properties

Molecular Formula	C8H18N2O3S
Molecular Weight	222.3051
Exact Mass	222.103
CAS #	83730-53-4
Related CAS #	DL-Buthionine-(S,R)-sulfoximine;5072-26-4;L-Buthionine-(S,R)-sulfoximine hydrochloride
PubChem CID	119565
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Boiling Point	382.3±52.0 °C at 760 mmHg
Melting Point	224-228ºC (dec.)
Flash Point	185.0±30.7 °C
Vapour Pressure	0.0±1.9 mmHg at 25°C
Index of Refraction	1.538
LogP	0.22
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	7
Heavy Atom Count	14
Complexity	284
Defined Atom Stereocenter Count	1
SMILES	CCCCS(=N)(=O)CC[C@@H](C(=O)O)N
InChi Key	KJQFBVYMGADDTQ-CVSPRKDYSA-N
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)/t7-,14?/m0/s1
Chemical Name	(2S)-2-amino-4-(butylsulfonimidoyl)butanoic acid
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	In ZAZ and M14 melanoma cell lines, 48 hours of treatment with L-buthionine-(S,R)-suLfoximine (BSO: 50 μM) led to a 95% reduction in GSH levels and a 60% reduction in GST enzyme activity. The cellular oxidative intermediate g-glutamine is induced in different cell lines by GST-π L-butyrine-(S,R)-suLfoximine (BSO) through irreversibly blocking g-glutamine cysteine synthetase Amide protein and mRNA levels were drastically reduced [1]. An enzyme called semiphosphatidylamine synthetase is necessary for the production of glutathione (GSH) [2]. Ferroptosis is induced by L-butanthionine-(S,R)-suLfoximine (BSO) [3].
ln Vivo	In developing mice, BSO raises the frequency of DNA. In comparison to animals that were not treated, BSO therapy decreased GSH levels in mice that were given 2 mM and 20 mM BSO, respectively, by 55% and 70%. GSH was outpaced by co-treatment with 2 mM BSO and 20 mM NAC. The degree is comparable to that of 2 mM BSO, which is in line with BSO's ability to inhibit the g-GCS enzyme, which is responsible for the synthesis of dyes from GSH. C57BL/6J pun/pun mice are an animal model for cysteine modules, similar to GSH, following BSO therapy [2].
Animal Protocol	Animal/Disease Models: C57BL/6J pun/pun mice[2]. Doses: 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. Route of Administration: Drinking water Experimental Results: The average number of eye-spots (mean±SEM) is 5.36±0.29 (n=46), 7.79±0.45 (n=34) and 8.78±0.61 (n=32) in untreated controls, 2 mM L-Buthionine-(S,R)-sulfoximine (BSO) and 20 mM BSO treated mice, respectively. The 2 mM BSO treatment results in ~30% more eye-spots, and the 20 mM treatment results in 40% more eye-spots compared with untreated mice.
References	[1]. 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]. Glutathione depletion by buthionine sulfoximine induces DNA deletions in mice. Carcinogenesis. 2006 Feb;27(2):240-4. [3]. Low tumor glutathione level as a sensitivity marker for glutamate-cysteine ligase inhibitors. Oncol Lett. 2018 Jun;15(6):8735-8743.
Additional Infomation	L-buthionine-(S,R)-sulfoximine is a 2-amino-4-(S-butylsulfonimidoyl)butanoic acid which has S-configuration. It is a inhibitor of gamma-glutamylcysteine synthetase and glutathione (GSH) biosynthesis and is capable of enhancing the apoptotic effects of several chemotherapeutic agents. It has a role as a ferroptosis inducer and an EC 6.3.2.2 (glutamate--cysteine ligase) inhibitor. Buthionine Sulfoximine is a synthetic amino acid. Buthionine sulfoximine irreversibly inhibits gamma-glutamylcysteine synthase, thereby depleting cells of glutathione, a metabolite that plays a critical role in protecting cells against oxidative stress, and resulting in free radical-induced apoptosis. Elevated glutathione levels are associated with tumor cell resistance to alkylating agents and platinum compounds. By depleting cells of glutathione, this agent may enhance the in vitro and in vivo cytotoxicities of various chemotherapeutic agents in drug-resistant tumors. Buthionine sulfoximine may also exhibit antiangiogenesis activity. (NCI04)

Solubility Data

Solubility (In Vitro)	H2O : ~18.33 mg/mL (~82.45 mM) DMSO :< 1 mg/mL
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	4.4982 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

*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.