Details
| Stereochemistry | MIXED |
| Molecular Formula | C8H18N2O3S |
| Molecular Weight | 222.305 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCCS(=N)(=O)CCC(N)C(O)=O
InChI
InChIKey=KJQFBVYMGADDTQ-UHFFFAOYSA-N
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)
| Molecular Formula | C8H18N2O3S |
| Molecular Weight | 222.305 |
| Charge | 0 |
| Count |
|
| Stereochemistry | RACEMIC |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Optical Activity | ( + / - ) |
Buthionine sulfoximine (BSO) is a selective inhibitor of γ-glutamylcysteine synthetase (γ-GCS), the rate-limiting enzyme in glutathione (GSH) synthesis. In cancer cells, glutathione depletion significantly increased cytotoxicity via oxidative stress. In addition, in neuroblastoma cells susceptible to Buthionine sulfoximine treatment, DNA damage and cell apoptosis occurred via ROS production. Buthionine sulfoximine plus melphalan was effective in treatment for patients with recurrent/refractory neuroblastoma. Buthionine sulfoximine may also be used to increase the sensitivity of parasites to oxidative antiparasitic drugs. Buthionine sulfoximine has been shown to increase the efficacy of nifurtimox against T. cruzi and has also been shown to be an effective modulator of GSH-mediated chemoresistance by increasing the in vitro cytotoxicity of alkylating agents and radiation. Buthionine sulfoximine has been tested in animal studies and in human phase I trials for adults with solid tumors, with documented clinical responses in patients with melanoma, ovarian carcinoma and small cell carcinoma of the lung treated with the combination of Buthionine sulfoximine and melphalan.
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
650 μM |
750 mg/m²/h other, intravenous dose: 750 mg/m²/h route of administration: Intravenous experiment type: OTHER co-administered: MELPHALAN |
BUTHIONINE SULFOXIMINE serum | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
530 μM |
750 mg/m²/h other, intravenous dose: 750 mg/m²/h route of administration: Intravenous experiment type: OTHER co-administered: MELPHALAN |
BUTHIONINE SULFOXIMINE serum | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
465 μM |
750 mg/m²/h other, intravenous dose: 750 mg/m²/h route of administration: Intravenous experiment type: OTHER co-administered: MELPHALAN |
BUTHIONINE SULFOXIMINE serum | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1260 μM |
1500 mg/m²/h other, intravenous dose: 1500 mg/m²/h route of administration: Intravenous experiment type: OTHER co-administered: MELPHALAN |
BUTHIONINE SULFOXIMINE serum | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
18.5 mM × h |
750 mg/m²/h other, intravenous dose: 750 mg/m²/h route of administration: Intravenous experiment type: OTHER co-administered: MELPHALAN |
BUTHIONINE SULFOXIMINE serum | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
28.2 mM × h |
750 mg/m²/h other, intravenous dose: 750 mg/m²/h route of administration: Intravenous experiment type: OTHER co-administered: MELPHALAN |
BUTHIONINE SULFOXIMINE serum | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
31.3 mM × h |
750 mg/m²/h other, intravenous dose: 750 mg/m²/h route of administration: Intravenous experiment type: OTHER co-administered: MELPHALAN |
BUTHIONINE SULFOXIMINE serum | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
61.8 mM × h |
1500 mg/m²/h other, intravenous dose: 1500 mg/m²/h route of administration: Intravenous experiment type: OTHER co-administered: MELPHALAN |
BUTHIONINE SULFOXIMINE serum | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
37 min |
750 mg/m²/h other, intravenous dose: 750 mg/m²/h route of administration: Intravenous experiment type: OTHER co-administered: MELPHALAN |
BUTHIONINE SULFOXIMINE serum | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
46 min |
750 mg/m²/h other, intravenous dose: 750 mg/m²/h route of administration: Intravenous experiment type: OTHER co-administered: MELPHALAN |
BUTHIONINE SULFOXIMINE serum | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
30 min |
750 mg/m²/h other, intravenous dose: 750 mg/m²/h route of administration: Intravenous experiment type: OTHER co-administered: MELPHALAN |
BUTHIONINE SULFOXIMINE serum | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
32 min |
1500 mg/m²/h other, intravenous dose: 1500 mg/m²/h route of administration: Intravenous experiment type: OTHER co-administered: MELPHALAN |
BUTHIONINE SULFOXIMINE serum | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Transcription factor Nrf2 mediates an adaptive response to sulforaphane that protects fibroblasts in vitro against the cytotoxic effects of electrophiles, peroxides and redox-cycling agents. | 2009-06-15 |
|
| Oxidative stress and sodium methyldithiocarbamate-induced modulation of the macrophage response to lipopolysaccharide in vivo. | 2009-06 |
|
| Differential protection by human glutathione S-transferase P1 against cytotoxicity of benzo[a]pyrene, dibenzo[a,l]pyrene, or their dihydrodiol metabolites, in bi-transgenic cell lines that co-express rat versus human cytochrome P4501A1. | 2009-05-15 |
|
| Early sensing and gene expression profiling under a low dose of cadmium exposure. | 2009-03 |
|
| Involvement of oxidative stress and activation of aryl hydrocarbon receptor in elevation of CYP1A1 expression and activity in lung cells and tissues by arsenic: an in vitro and in vivo study. | 2009-02 |
|
| The hepatotoxic metabolite of acetaminophen directly activates the Keap1-Nrf2 cell defense system. | 2008-10 |
|
| Elevated GSH level increases cadmium resistance through down-regulation of Sp1-dependent expression of the cadmium transporter ZIP8. | 2008-09 |
|
| NF-kappaB and AP-1 are key signaling pathways in the modulation of NAD(P)H:quinone oxidoreductase 1 gene by mercury, lead, and copper. | 2008-08-30 |
|
| Metallothionein alleviates glutathione depletion-induced oxidative cardiomyopathy in murine hearts. | 2008-07 |
|
| Oxidative stress regulates type 3 deiodinase and type 2 deiodinase in cultured rat astrocytes. | 2008-07 |
|
| Heme-oxygenase 1 gene expression is a marker for hexavalent chromium-induced stress and toxicity in human dermal fibroblasts. | 2008-06 |
|
| Markers of electrophilic stress caused by chemically reactive metabolites in human hepatocytes. | 2008-05 |
|
| The role of redox-sensitive transcription factors NF-kappaB and AP-1 in the modulation of the Cyp1a1 gene by mercury, lead, and copper. | 2008-03-01 |
|
| Activation of Nrf2-mediated oxidative stress response in macrophages by hypochlorous acid. | 2008-02-01 |
|
| Decreased glutathione levels potentiate the apoptotic efficacy of selenium: possible involvement of p38 and JNK MAPKs--in vitro studies. | 2008-02 |
|
| Changes in antioxidant defense systems induced by thiram in V79 Chinese hamster fibroblasts. | 2008-02 |
|
| Boric acid inhibits LPS-induced TNF-alpha formation through a thiol-dependent mechanism in THP-1 cells. | 2008 |
|
| Activation of nuclear factor (erythroid-2 like) factor 2 by toxic bile acids provokes adaptive defense responses to enhance cell survival at the emergence of oxidative stress. | 2007-11 |
|
| Accumulation of hypoxia-inducible factor-1alpha through a novel electrophilic, thiol antioxidant-sensitive mechanism. | 2007-10 |
|
| De novo synthesis of glutathione is a prerequisite for curcumin to inhibit hepatic stellate cell (HSC) activation. | 2007-08-01 |
|
| Effects of BSO, GSH, Vit-C and DMPS on the nephrotoxicity of mercury. | 2007-08 |
|
| Curcumin-induced GADD153 upregulation: modulation by glutathione. | 2007-05-15 |
|
| Expression and function of cystine/glutamate transporter in neutrophils. | 2007-04 |
|
| Chalcone inhibits the activation of NF-kappaB and STAT3 in endothelial cells via endogenous electrophile. | 2007-03-20 |
|
| Polycyclic aromatic hydrocarbon (PAH) metabolizing enzyme activities in human lung, and their inducibility by exposure to naphthalene, phenanthrene, pyrene, chrysene, and benzo(a)pyrene as shown in the rat lung and liver. | 2007-03 |
|
| Increased expression of the MGMT repair protein mediated by cysteine prodrugs and chemopreventative natural products in human lymphocytes and tumor cell lines. | 2007-02 |
|
| Effect of various radical generators on insulin-dependent regulation of hepatic gene expression. | 2007-01 |
|
| Co-operative effect of glutathione depletion and selenium induced oxidative stress on API and NFkB expression in testicular cells in vitro: insights to regulation of spermatogenesis. | 2007 |
|
| Buthionine sulfoximine enhancement of arsenic trioxide-induced apoptosis in leukemia and lymphoma cells is mediated via activation of c-Jun NH2-terminal kinase and up-regulation of death receptors. | 2006-12-01 |
|
| Curcumin inhibits hypoxia-inducible factor-1 by degrading aryl hydrocarbon receptor nuclear translocator: a mechanism of tumor growth inhibition. | 2006-11 |
|
| Inducible nitric oxide synthase up-regulation and mitochondrial glutathione depletion mediate cyanide-induced necrosis in mesencephalic cells. | 2006-10 |
|
| Oxidative stress induces phosphoenolpyruvate carboxykinase expression in H4IIE cells. | 2006-09 |
|
| Upregulation of endothelial heme oxygenase-1 expression through the activation of the JNK pathway by sublethal concentrations of acrolein. | 2006-08-01 |
|
| Regulation of apoptosis/necrosis execution in cadmium-treated human promonocytic cells under different forms of oxidative stress. | 2006-05 |
|
| Superoxide anions and hydrogen peroxide induce hepatocyte death by different mechanisms: involvement of JNK and ERK MAP kinases. | 2006-05 |
|
| The novel antioxidant 3-O-caffeoyl-1-methylquinic acid induces Nrf2-dependent phase II detoxifying genes and alters intracellular glutathione redox. | 2006-04-15 |
|
| O(6)-methylguanine DNA-methyltransferase (MGMT) overexpression in melanoma cells induces resistance to nitrosoureas and temozolomide but sensitizes to mitomycin C. | 2006-03-01 |
|
| Redox control of K+ channel remodeling in rat ventricle. | 2006-03 |
|
| Piceatannol upregulates endothelial heme oxygenase-1 expression via novel protein kinase C and tyrosine kinase pathways. | 2006-02 |
|
| Antimony trioxide-induced apoptosis is dependent on SEK1/JNK signaling. | 2006-01-05 |
|
| Schisandrin B-induced increase in cellular glutathione level and protection against oxidant injury are mediated by the enhancement of glutathione synthesis and regeneration in AML12 and H9c2 cells. | 2006 |
|
| The role of low molecular weight thiols in T lymphocyte proliferation and IL-2 secretion. | 2005-12-15 |
|
| Inhibition of interferon-gamma signaling by a mercurio-substituted dihydropsoralen in murine keratinocytes. | 2005-12-05 |
|
| The role of oxidative stress in the modulation of aryl hydrocarbon receptor-regulated genes by As3+, Cd2+, and Cr6+. | 2005-12-01 |
|
| Arsenite enhances tumor necrosis factor-alpha-induced expression of vascular cell adhesion molecule-1. | 2005-11-15 |
|
| Preventive mechanism of cellular glutathione in monomethylarsonic acid-induced cytolethality. | 2005-08-01 |
|
| Heme oxygenase-2 protects against glutathione depletion-induced neuronal apoptosis mediated by bilirubin and cyclic GMP. | 2005-04 |
|
| Two major branches of anti-cadmium defense in the mouse: MTF-1/metallothioneins and glutathione. | 2005 |
|
| An improved model of acetaminophen-induced fulminant hepatic failure in dogs. | 1992-02 |
|
| In vivo nephrotoxicity induced in mice by chromium(VI). Involvement of glutathione and chromium(V). | 1991-10 |
Patents
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 21:40:06 GMT 2025
by
admin
on
Mon Mar 31 21:40:06 GMT 2025
|
| Record UNII |
LW4108Q0BV
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
-
Download
| Name | Type | Language | ||
|---|---|---|---|---|
|
Preferred Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English |
| Classification Tree | Code System | Code | ||
|---|---|---|---|---|
|
FDA ORPHAN DRUG |
209705
Created by
admin on Mon Mar 31 21:40:06 GMT 2025 , Edited by admin on Mon Mar 31 21:40:06 GMT 2025
|
||
|
NCI_THESAURUS |
C2130
Created by
admin on Mon Mar 31 21:40:06 GMT 2025 , Edited by admin on Mon Mar 31 21:40:06 GMT 2025
|
||
|
FDA ORPHAN DRUG |
213205
Created by
admin on Mon Mar 31 21:40:06 GMT 2025 , Edited by admin on Mon Mar 31 21:40:06 GMT 2025
|
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
28714
Created by
admin on Mon Mar 31 21:40:06 GMT 2025 , Edited by admin on Mon Mar 31 21:40:06 GMT 2025
|
PRIMARY | |||
|
100000172386
Created by
admin on Mon Mar 31 21:40:06 GMT 2025 , Edited by admin on Mon Mar 31 21:40:06 GMT 2025
|
PRIMARY | |||
|
DTXSID6044434
Created by
admin on Mon Mar 31 21:40:06 GMT 2025 , Edited by admin on Mon Mar 31 21:40:06 GMT 2025
|
PRIMARY | |||
|
LW4108Q0BV
Created by
admin on Mon Mar 31 21:40:06 GMT 2025 , Edited by admin on Mon Mar 31 21:40:06 GMT 2025
|
PRIMARY | |||
|
D019328
Created by
admin on Mon Mar 31 21:40:06 GMT 2025 , Edited by admin on Mon Mar 31 21:40:06 GMT 2025
|
PRIMARY | |||
|
DB12870
Created by
admin on Mon Mar 31 21:40:06 GMT 2025 , Edited by admin on Mon Mar 31 21:40:06 GMT 2025
|
PRIMARY | |||
|
381100
Created by
admin on Mon Mar 31 21:40:06 GMT 2025 , Edited by admin on Mon Mar 31 21:40:06 GMT 2025
|
PRIMARY | |||
|
m2798
Created by
admin on Mon Mar 31 21:40:06 GMT 2025 , Edited by admin on Mon Mar 31 21:40:06 GMT 2025
|
PRIMARY | Merck Index | ||
|
21157
Created by
admin on Mon Mar 31 21:40:06 GMT 2025 , Edited by admin on Mon Mar 31 21:40:06 GMT 2025
|
PRIMARY | |||
|
BUTHIONINE SULFOXIMINE
Created by
admin on Mon Mar 31 21:40:06 GMT 2025 , Edited by admin on Mon Mar 31 21:40:06 GMT 2025
|
PRIMARY | |||
|
5072-26-4
Created by
admin on Mon Mar 31 21:40:06 GMT 2025 , Edited by admin on Mon Mar 31 21:40:06 GMT 2025
|
PRIMARY |
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
|
ACTIVE MOIETY |
