BUTHIONINE SULFOXIMINE

Investigational

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

Structure Search

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)

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Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28362858 | https://www.ncbi.nlm.nih.gov/pubmed/28115164 | https://www.ncbi.nlm.nih.gov/pubmed/27282514

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.

Originator

Approval Year

PubMed

Title	Date	PubMed
Hepatocellular response to chemical stress in CD-1 mice: induction of early genes and gamma-glutamylcysteine synthetase.	2000 Aug	10915739
Arsenic trioxide-induced apoptosis and differentiation are associated respectively with mitochondrial transmembrane potential collapse and retinoic acid signaling pathways in acute promyelocytic leukemia.	2000 Feb	10673743
Induction of oxidative stress by glutathione depletion causes severe hypertension in normal rats.	2000 Jul	10904027
Inducers of gamma-glutamylcysteine synthetase and their effects on glutathione synthetase expression.	2000 Sep 7	10978506
Inhibition of cell proliferation and AP-1 activity by acrolein in human A549 lung adenocarcinoma cells due to thiol imbalance and covalent modifications.	2002 Feb	11849044
Mediation of cadmium-induced oxidative damage and glucose-6-phosphate dehydrogenase expression through glutathione depletion.	2003	12717738
Synthesis and antifilarial evaluation of N1,Nn- xylofuranosylated diaminoalkanes.	2003 Apr 17	12659765
Oxidative modulation of the glutathione-redox couple enhances lipopolysaccharide-induced interleukin 12 P40 production by a mouse macrophage cell line, J774A.1.	2003 Mar	12688424
Regulation of glutathione in cardiac myocytes.	2003 Sep	12967637
Oxidative stimuli affect polyglutamine aggregation and cell death in human mutant ataxin-1-expressing cells.	2003 Sep 4	12893416
[CD59 mutation and DNA oxidative damage in A(L) cells induced by crocidolite fibers].	2004 Feb	15033018
Alteration of cellular phenotype and responses to oxidative stress by manganese superoxide dismutase and a superoxide dismutase mimic in RWPE-2 human prostate adenocarcinoma cells.	2004 Jun	15130278
JNK activation is a mediator of arsenic trioxide-induced apoptosis in acute promyelocytic leukemia cells.	2004 May 1	14701702
1-Benzyl-1,2,3,4-tetrahydroisoquinoline, a Parkinsonism-inducing endogenous toxin, increases alpha-synuclein expression and causes nuclear damage in human dopaminergic cells.	2004 May 15	15114628
Spatial activities and induction of glutamate-cysteine ligase (GCL) in the postimplantation rat embryo and visceral yolk sac.	2004 Oct	15115889
Preventive mechanism of cellular glutathione in monomethylarsonic acid-induced cytolethality.	2005 Aug 1	15963344
Garlic oil and DDB, comprised in a pharmaceutical composition for the treatment of patients with viral hepatitis, prevents acute liver injuries potentiated by glutathione deficiency in rats.	2005 Jun 30	15950962
Upregulation of endothelial heme oxygenase-1 expression through the activation of the JNK pathway by sublethal concentrations of acrolein.	2006 Aug 1	16480751
Regulation of apoptosis/necrosis execution in cadmium-treated human promonocytic cells under different forms of oxidative stress.	2006 May	16532269
Expression and function of cystine/glutamate transporter in neutrophils.	2007 Apr	17200146
Boric acid inhibits LPS-induced TNF-alpha formation through a thiol-dependent mechanism in THP-1 cells.	2008	18755394
Activation of Nrf2-mediated oxidative stress response in macrophages by hypochlorous acid.	2008 Feb 1	17980396
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 Jul-Aug	18752316
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 Feb	19033395

Patents

Sample Use Guides

In Vivo Use Guide

3 gm/M2 given over 30 minutes followed by a continuous infusion of 1 gm/M2/hour for 72 hours (total 72.5 hours).Total daily infusion dose (minus the initial bolus)will be 24 gm/m2/day

Route of Administration: Intravenous

Name

Type

Language

BUTHIONINE SULFOXIMINE

Common Name

English

BUTIONINE SULFOXIMINE

Common Name

English

BUTHIONINE SULFOXAMINE

Common Name

English

BUTANOIC ACID, 2-AMINO-4-(S-BUTYLSULFONIMIDOYL)-

Common Name

English

NSC-381100

Code

English

Buthionine sulfoximine [WHO-DD]

Common Name

English

DL-BUTHIONINE (S,R)-SULFOXIMINE

Common Name

English

BUTHIONINE SULFOXIMINE [MI]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

209705