D,L-Buthionine-(S,R)-sulfoximine

Names

[ Name ]:
D,L-Buthionine-(S,R)-sulfoximine

[Synonym ]:
2-amino-4-(butylsulfonimidoyl)butanoic acid
DL-Buthionine (S,R)-sulfoximine
EINECS 246-685-1
MFCD00070309
D,L-Buthionine-(S,R)-sulfoximine

Biological Activity

[Description]:

D,L-Buthionine-(S,R)-sulfoximine is a potent inhibitor of glutamylcysteine synthetase biosynthesis.

[Related Catalog]:

Signaling Pathways >> Others >> Others

Research Areas >> Cancer

[Target]

glutamylcysteine synthetase[1]

[In Vitro]

Buthionine sulfoximine is an analogs of methionine sulfoximine and inhibits gamma-glutamylcysteine synthetase about 20 times more effectively than prothionine sulfoximine and at least 100 times more effectively than methionine sulfoximine[1].

[In Vivo]

Treatment of mice bearing HT1080 and HT1080/DR4 xenografts with a continuous i.v infusion of nontoxic doses of D,L-Buthionine-(S,R)-sulfoximine (300 and 600 mg/kg/day) produce a 60% reduction of GSH plasma levels and greater than 95 % reduction in GSH tumor levels in both parental and multidrug-resistant tumors[2].

[Animal admin]

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.

[2]. Vanhoefer U, et al. 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.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.29g/cm3

[ Boiling Point ]:
382.3ºC at 760 mmHg

[ Melting Point ]:
215ºC (dec.)(lit.)

[ Molecular Formula ]:
C₈H₁₈N₂O₃S

[ Molecular Weight ]:
222.30500

[ Flash Point ]:
185ºC

[ Exact Mass ]:
222.10400

[ PSA ]:
112.62000

[ LogP ]:
2.30100

[ Index of Refraction ]:
1.537

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
H2O: 50 mg/mL, clear, colorless

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: EK7713435

CHEMICAL NAME :: Butanoic acid, 2-amino-4-(S-butylsulfonimidoyl)-

CAS REGISTRY NUMBER :: 5072-26-4

LAST UPDATED :: 199612

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C8-H18-N2-O3-S

MOLECULAR WEIGHT :: 222.34

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 1 gm/kg

SEX/DURATION :: female 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Maternal Effects - other effects

REFERENCE :: REPTED Reproductive Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1987- Volume(issue)/page/year: 6,133,1992

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi

[ Risk Phrases ]:
36/37/38

[ Safety Phrases ]:
26-36

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
EK7713435

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