OXIGLUTATIONE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H32N6O12S2
Molecular Weight	612.631
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

N[C@@H](CCC(=O)N[C@@H](CSSC[C@H](NC(=O)CC[C@H](N)C(O)=O)C(=O)NCC(O)=O)C(=O)NCC(O)=O)C(O)=O

InChI

InChIKey=YPZRWBKMTBYPTK-BJDJZHNGSA-N

InChI=1S/C20H32N6O12S2/c21-9(19(35)36)1-3-13(27)25-11(17(33)23-5-15(29)30)7-39-40-8-12(18(34)24-6-16(31)32)26-14(28)4-2-10(22)20(37)38/h9-12H,1-8,21-22H2,(H,23,33)(H,24,34)(H,25,27)(H,26,28)(H,29,30)(H,31,32)(H,35,36)(H,37,38)/t9-,10-,11-,12-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://pubchem.ncbi.nlm.nih.gov/compound/oxiglutatione
Curator's Comment: description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/6137189

Oxiglutathione is the oxidized disulfide form of glutathione (GSH) with potential protective activity. Glutathione disulfide (GSSG) is reduced by glutathione reductase to GSH. GSSG and GSH together play important roles in numerous redox reactions, such as those involved in the detoxification of harmful substances and free radicals, and in reactions preventing oxidative damage in erythrocytes. Upon ocular administration in irrigation solution, glutathione disulfide may exert a beneficial effect on the intracellular redox state of glutathione, thereby protecting the integrity and barrier function of the corneal endothelial cells.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glutathione reductase 11 Target ID: CHEMBL2755 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6137189	Substrate 661

Conditions

Condition	Modality	Targets	Highest Phase	Product
Dry eye syndrome 21 Sources: http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM248780.pdf	Preventing		Approved 8583	NAVSTEL Approved Use Navstel is a sterile intraocular irrigating solution for use during all surgical procedures, including those requiring a relatively long intraocular perfusion time (e.g. vitrectomy, extracapsular cataract extraction/lens aspiration, anterior segment reconstruction, etc.). Upon ocular administration in irrigation solution, oxiglutathione disulfide exerts a beneficial effect on the intracellular redox state of glutathione, thereby protecting the integrity and barrier function of the corneal endothelial cells. Launch Date 2008

C_max

Value	Dose	Co-administered	Analyte	Population
0.65 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20359856/	250 mg/kg single, intraperitoneal dose: 250 mg/kg route of administration: Intraperitoneal experiment type: SINGLE co-administered:		OXIGLUTATIONE plasma	Mus musculus population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
1.18 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20359856/	250 mg/kg single, intraperitoneal dose: 250 mg/kg route of administration: Intraperitoneal experiment type: SINGLE co-administered:		OXIGLUTATIONE plasma	Mus musculus population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
13 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20359856/	250 mg/kg single, intraperitoneal dose: 250 mg/kg route of administration: Intraperitoneal experiment type: SINGLE co-administered:		OXIGLUTATIONE plasma	Mus musculus population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

Doses

Dose	Population	Adverse events
10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	Other AEs: Increased intraocular pressure, Headache... Other AEs: Increased intraocular pressure (12%) Headache (3%) Ocular discomfort (5%) Macular edema (4%) Conjunctival hyperemia (4%) Dry eye (3%) Iritis (3%) Retinal hemorrhage (3%) Vision blurred (2%) Posterior capsule opacification (2%) Cataract (11%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf

AEs

AE	Significance	Dose	Population
Cataract	11%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Increased intraocular pressure	12%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Posterior capsule opacification	2%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Vision blurred	2%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Dry eye	3%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Headache	3%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Iritis	3%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Retinal hemorrhage	3%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Conjunctival hyperemia	4%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Macular edema	4%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Ocular discomfort	5%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChemIDplus	103239243	https://chem.nlm.nih.gov/chemidplus/id/0103239243
PubChem	76967787	https://pubchem.ncbi.nlm.nih.gov/compound/76967787

PubMed

Title	Date	PubMed
Effect of DL-alpha-lipoic acid on mitochondrial enzymes in aged rats.	2001-11-28	11672700
Differences in basal airway antioxidant concentrations are not predictive of individual responsiveness to ozone: a comparison of healthy and mild asthmatic subjects.	2001-10-15	11595381
A sensitive and specific assay for glutathione with potential application to glutathione disulphide, using high-performance liquid chromatography-tandem mass spectrometry.	2001-10-05	11589454
COPD as a muscle disease.	2001-10-01	11673186
Redox-mediated effects of selenium on apoptosis and cell cycle in the LNCaP human prostate cancer cell line.	2001-10-01	11585738
Induction of mild intracellular redox imbalance inhibits proliferation of CaCo-2 cells.	2001-10	11641239
Glutathione stability in whole blood: effects of various deproteinizing acids.	2001-10	11591901
The functions of inter- and intracellular glutathione transport systems in plants.	2001-10	11590068
Thiols and polyamines in the potentiation of malathion toxicity in larval stages of the toad Bufo arenarum.	2001-10	11574288
Erythrocytic glutathione and plasma cysteine status of human immunodeficient patients.	2001-10	11568311
Resuscitation with 100% oxygen: should we change our ways?	2001-10	11568283
Redox regulation of endothelial barrier integrity.	2001-10	11557591
Inhibition of rat PC12 cell calpain activity by glutathione, oxidized glutathione and nitric oxide.	2001-09-28	11567795
Antioxidant defense disruption by polycyclic aromatic hydrocarbons-coated onto Fe(2)O(3) particles in human lung cells (A549).	2001-09-25	11543909
A new and versatile method for determination of thiolamines of biological importance.	2001-09-15	11585123
Application of double-impedance system and cyclic voltammetry to study the adsorption of fullerols (C60(OH)n) on biological peptide-adsorbed gold electrode.	2001-09	11516084
Enhanced mitochondrial testicular antioxidant capacity in Goto-Kakizaki diabetic rats: role of coenzyme Q.	2001-09	11502580
Effect of benzoyl peroxide on antioxidant status, NF-kappaB activity and interleukin-1alpha gene expression in human keratinocytes.	2001-08-28	11522381
Cooperative action of antioxidant defense systems in Drosophila.	2001-08-21	11525742
Interaction of pyridostigmine and physical stress on antioxidant defense system in skeletal muscle of mice.	2001-08-02	11481669
Non-enzymatic antioxidative defence mechanisms against reactive oxygen species in bovine-retained and not-retained placenta: vitamin C and glutathione.	2001-08	11555370
Crayfish Procambarus clarkii shows circadian variations in different parameters of the GSH cycle.	2001-08	11547576
An integrated electrochemical capillary liquid chromatography-dual microelectrode system for bromine based reaction detection.	2001-08	11534588
Short- and long-term effects of dehydroascorbate in Lupinus albus and Allium cepa roots.	2001-08	11522912
Protective effect of melatonin against adriamycin toxicity in the rat.	2001-08	11485001
A comparative study of glutathione and ascorbate metabolism during germination of Pinus pinea L. seeds.	2001-08	11479329
Determination of blood total, reduced, and oxidized glutathione in pediatric subjects.	2001-08	11468240
Vascular and hepatocellular peroxynitrite formation during acetaminophen toxicity: role of mitochondrial oxidant stress.	2001-08	11452133
An ion exchange liquid chromatography/mass spectrometry method for the determination of reduced and oxidized glutathione and glutathione conjugates in hepatocytes.	2001-08	11451650
Regulation of the plant-type 5'-adenylyl sulfate reductase by oxidative stress.	2001-07-31	11467967
Modulation of rat liver mitochondrial antioxidant defence system by thyroid hormone.	2001-07-27	11476958
Thiols prevent H2O2-mediated loss of sperm motility in cryopreserved bull semen.	2001-07-15	11480619
[Effect of reduced and oxidized glutathione on physico-chemical properties of erythrocyte membranes].	2001-07-14	11449546
Oxidative stress in zebrafish cells: potential utility of transgenic zebrafish as a deployable sentinel for site hazard ranking.	2001-07-02	11453295
Analysis of glutathione by capillary electrophoresis based on sample stacking.	2001-07	11504072
Effects of chronic N-acetylcysteine treatment on the actions of peroxynitrite on aortic vascular reactivity in hypertensive rats.	2001-07	11446713
Impairment of glutathione metabolism in human gastric epithelial cells treated with vacuolating cytotoxin from Helicobacter pylori.	2001-07	11427034
Nifedipine modulation of biliary GSH and GSSG/ conjugate efflux in normal and regenerating rat liver.	2001-07	11408258
Thiram-induced cytotoxicity is accompanied by a rapid and drastic oxidation of reduced glutathione with consecutive lipid peroxidation and cell death.	2001-06-21	11516525
Characterization of glutathione amide reductase from Chromatium gracile. Identification of a novel thiol peroxidase (Prx/Grx) fueled by glutathione amide redox cycling.	2001-06-15	11399772
Potential mechanisms for the inhibition of tumor cell growth by manganese superoxide dismutase.	2001-06	11491650
Lack of protective effect by intermittent hypoxia on MPTP-induced neurotoxicity in mice.	2001-06	11462788
A possible role of glutathione and glutathione disulfide in tracheary element differentiation in the cultured mesophyll cells of Zinnia elegans.	2001-06	11427688
Hydrogen peroxide removal and glutathione mixed disulfide formation during metabolic inhibition in mesencephalic cultures.	2001-06	11413233
Patients with allergic and irritant contact dermatitis are characterized by striking change of iron and oxidized glutathione status in nonlesional area of the skin.	2001-06	11407976
Glutathione deficiency intensifies ischaemia-reperfusion induced cardiac dysfunction and oxidative stress.	2001-05	11437734
Regulation of LPS induced IL-12 production by IFN-gamma and IL-4 through intracellular glutathione status in human alveolar macrophages.	2001-05	11422207
Aggregated proteins accelerate but do not increase the aggregation of D-glyceraldehyde-3-phosphate dehydrogenase. Specificity of protein aggregation.	2001-02	11563696
Time-dependent oxidative stress caused by benznidazole.	2001	11642718
Quantification of reduced and oxidized glutathione in whole blood samples by capillary electrophoresis.	2001	11427471

Patents

Sample Use Guides

In Vivo Use Guide

NAVSTEL solution, should be used according to the standard technique employed by the operating surgeon. Do not use NAVSTEL until Part I is fully reconstituted with Part II. Reconstitute just prior to surgery. After reconstitution, use a single patient administration set with an air-inlet in the plastic spike since the bottle does not contain a separate airway tube. Follow the directions for the particular administration set to be used. Insert the spike aseptically into the bottle through the center target area of the rubber stopper. Allow the fluid to flow to remove air from the tubing before intraocular irrigation begins. If a second bottle is necessary to complete the surgical procedure, insure that the vacuum is vented from the second bottle BEFORE attachment to the administration set.

Route of Administration: Irrigation

In Vitro Use Guide

Kinetic studies were carried out at 25 °C in a volume of 1 mL. The assay mixtures contained 100 mM potassium phosphate buffer pH 7.0, 200 mM KCl, 100 uM NADPH, and 1 mM GSSG. Inhibitor stock solutions were prepared in 100% DMSO. One % final DMSO concentration was kept constant in the assay cuvette. The reaction was started with the addition of the enzyme (8 milliunits or 1.2 pmol of FAD-containing subunit in 5 uL aliquot), and initial rates were determined from NADPH oxidation measured at 340 nm. Km for GSSG reduction was found to be 12.5 uM.

Name

Type

Language

OXIGLUTATIONE

Official Name

English

GLUTATHIONE DISULFIDE

Preferred Name

English

oxiglutatione [INN]

Common Name

English

GLUTATHIONE DISULPHIDE

Systematic Name

English

Oxiglutatione [WHO-DD]

Common Name

English

GLUTATHIONE DISULFIDE [MI]

Common Name

English

OXIGLUTATIONE [ORANGE BOOK]

Common Name

English

OXIGLUTATIONE [JAN]

Common Name

English

GLUTATHIONE DISULFIDE [ORANGE BOOK]

Common Name

English

GLUTATHIONE, DISULFIDE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C26170