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Aurothioglucose

HCID 6104
NotesReactions
Basic informationOverviewNames & identifiersPropertiesSafety & regulationChemistry & industryRelated reactionsCompound notes
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Basic information

CAS
12192-57-3
Standard SMILES
OC[C@H]1O[C@H]([S-])[C@H](O)[C@@H](O)[C@@H]1O.[Au+]
InChIKey
XHVAWZZCDCWGBK-WYRLRVFGSA-M
Molecular formula
C6H11AuO5S
Average molar mass
392.18 g/mol
Monoisotopic mass
391.99929

Overview

Aurothioglucose is a member of oxanes.

Names & identifiers

Preferred name
Aurothioglucose
IUPAC
gold(1+);(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxane-2-thiolate
English name
Aurothioglucose
Molecular formula
C6H11AuO5S
Molecular weight
392.18

Names & synonyms

AUROTHIOGLUCOSEGold thioglucoseSolganalSolganolAureotan12192-57-3AurumineAuthronBrenolOronolGlysanol BSolganal B
Show more names
GGTgtgGGTDGGT 1aurotanromosolCS-1197
(1-Thio-D-glucopyranosato)goldGold, (1-thio-D-glucopyranosato-O2,S1)-ThioglucosoaurateThioglucose, Gold2P2V9Q0E78Gold50B Oleosum, SolganalOleosum, Solganal B

Database identifiers

CAS
12192-57-3
PubChem CID
6104
ChEMBL
CHEMBL1697725
ChEBI
CHEBI:2930
EC Number
235-365-7

Properties

Computed structural properties

Topological polar surface area
91.2 Ų
Hydrogen bond donors
4
Hydrogen bond acceptors
6
Rotatable bonds
1
Heavy atoms
13
Formal charge
0
Complexity
160

Experimental & physicochemical properties

LogPlog Kow = -2.50
OdorSlight mercaptan-like odor
Color/FormYellow crystals
Solubility · 2 items

Slightly soluble in propylene glycol; practically insoluble in acetone, alcohol, chloroform, and ether

Soluble in water with decomposition.

Stability/Shelf LifeFollowing the date of manufacture, sterile aurothioglucose suspension ... /has an expiration date/ of 5 years.

Physicochemical properties

Melting point
107 oC · >107oC (dec.)
storage temp.
2 · 2-8°C
solubility
2 O: · H2O: soluble5mg/mL, clear
form
powder
color
white to beige
biological source
rabbit
Water Solubility
2 O: · H2O: 5mg/mL, clear

Safety & regulation

Safety information is for reference only and does not replace the supplier’s Safety Data Sheet (SDS), applicable regulations, or professional assessment.

GHS classification

GHS Classification · 5 items

This chemical does not meet GHS hazard criteria for 2% (1 of 49) of reports.

Danger

H317 (77.6%): May cause an allergic skin reaction [Warning Sensitization, Skin]

P203, P233, P260, P261, P271, P272, P280, P284, P302+P352, P304+P340, P318, P321, P333+P317, P342+P316, P362+P364, P403, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 49 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Hazard information

Regulatory InformationChemical: Gold, (1-thio-D-glucopyranosato)-
Other Safety InformationEvaluation - Chemicals not considered for in depth evaluation - Not commercially active in Australia
Hazard Classes and CategoriesSkin Sens. 1 (77.6%)

Safety & protection

Storage ConditionsSterile aurothioglucose suspension ... should be protected from light and stored at a temperature less than 40C, preferably at 1530C; freezing should be avoided.
Disposal Methods · 1 item

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Chemistry & industry

Pharmacology

ATC Code · 2 items

M - Musculo-skeletal system

QM - Musculo-skeletal system

Protein BindingIn plasma, 95-99% of the drug is bound to albumin fraction.
Pharmacodynamics · 1 item

After administration, patient serum levels of gold rise sharply but decline over the following week. Peak levels with aqueous preparations are higher and decline faster than those with oily preparations. Regular weekly administration produces a continuous rise in the basal value for several months, after which the serum level becomes relatively stable. After a standard weekly dose, considerable individual variation in the levels of gold can be observed. A steady decline in gold levels occurs when the interval between injections is lengthened, and small amounts may be found in the serum for months after discontinuation of therapy. The incidence of toxic reactions is seemingly unrelated to the plasma level of gold, but may perhaps be more associated with the total cumulative content of gold in the body.

Mechanism of Action · 3 items

Rheumatoid arthritis is an autoimmune disease in which the body's immune system mistakenly attacks the lining of various skeletal bone joints of the body. These attacks are facilitated by various pro-inflammatory immune cells and agents like cytokines, histamines, mast cells, macrophages, monocytes, lymphocytes, leukocytes, and many others. The longterm result of this unwanted immune response is chronic inflammation and painful tissue damage. The cause of the malfunctioning immune system in rheumatoid arthritis is unknown and there is no definitive cure for the condition. Similarly, the mechanism of action of aurothioglucose is also not well elucidated. Nevertheless, some studies have suggested that the combination of both the sulfhydryl ligand and aureus cation present in aurothioglucose elicits an inhibitory effect on adenylyl cyclase activity in human lymphocyte membranes and in membranes of T and B lymphocyte subsets. In particular, such inhibition of the activity of adenylyl cyclase and its various isoforms would theoretically also limit the cyclases' ability to induce mast cell degranulation and histamine release, to enhance respiratory burst effects, to stimulate the action of resting macrophages, to induce and activate phagocytes, to induce neutrophil chemotaxis, etc. - all of which are pro-inflammatory actions.

Related reactions

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Compound notes

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On this pageBasic informationOverviewNames & identifiersPropertiesSafety & regulationChemistry & industryRelated reactionsCompound notes
Merck
13 · 13,887
Stability
Hygroscopic, Light Sensitive
InChI
1S/C6H12O5S.Au.H2O/c7-1-2-3(8)4(9)5(10)6(12)11-2;;/h2-10,12H,1H2;;1H2/q;+1;/p-1/t2-,3-,4+,5-,6-;;/m1../s1
InChIKey
SGVIEHTYEMEDRR-PKXGBZFFSA-M
SMILES
O.OC[C@H]1O[C@H](S[Au])[C@H](O)[C@@H](O)[C@@H]1O
FDA UNII
2 P2V9Q0E78 · 2P2V9Q0E78
ATC code
1 CB04 · M01CB04
IARC
3 · 3 (Vol. 13, Sup 7) 1987
EPA Substance Registry System
Aurothioglucose (12192-57-3)
UNSPSC Code
41116107 · 41116107
NACRES
77 · NA.77
Symbol(GHS)
7 · GHS07
Signal word
Warning
Hazard statements
317 · H317-H412
Precautionary statements
261 · P261-P272-P273-P280-P302+P352-P333+P313
PPE
95 · dust mask type N95 (US), Eyeshields, Faceshields, Gloves
Hazard Codes
Xn
Risk Statements
42 · 42/43
Safety Statements
22 · 22-36/37-45
RIDADR
2811 · 2811
WGK Germany
3 · 3
HazardClass
6.1 · 6.1(b)
PackingGroup
III
HS Code
2843300000 · 2843300000
Storage Class
11 · 11 - Combustible Solids
Hazard Classifications
1 Skin · Resp. Sens. 1Skin Sens. 1
Hazardous Substances Data
12192 · 12192-57-3(Hazardous Substances Data)
Toxicity
50 intravenous · LD50 intravenous in chicken: 1gm/kg

Toxicology

Milk ConcentrationsSmall amounts of gold have been shown to be distributed into milk in women receiving aurothioglucose ... .
Medical Surveillance · 1 item

Although rare, blood dyscrasias including granulocytopenia, agranulocytosis, thrombocytopenia with or without purpura, leukopenia, eosinophilia, panmyelopathy, hemorrhagic diathesis, and hypoplastic and aplastic anemia, have been reported. These reactions may occur separately or in combination.

Human Toxicity Excerpts · 2 items

/SIGNS AND SYMPTOMS/ Dermatitis is the most common reaction. Pruritus should be considered a warning signal of an impending cutaneous reaction. Erythema and occasionally the more severe reactions such as popular, vesicular, and exfoliative dermatitis leading to alopecia and shedding of the nails may occur. Chrysiasis (gray-to-blue pigmentation) has been reported, especially in photo-exposed areas. Gold dermatitis may be aggravated by exposure to sunlight, or an actinic rash may develop.

/SIGNS AND SYMPTOMS/ Less common but more severe effects that may occur shortly after injection or at any time in gold therapy include: anaphylactic shock, syncope, bradycardia, thickening of the tongue, difficulty in swallowing and breathing, and angioneurotic edema. If they are observed, treatment with Solganal suspension should be discontinued.

Carcinogen Classification · 5 items

Aurothioglucose

Group 3: Not classifiable as to its carcinogenicity to humans

Volume 13: (1977) Some Miscellaneous Pharmaceutical Substances

1987

1987

Drug Induced Liver Injury · 5 items

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

aurothioglucose

DILI Positive

Intramuscular

DOI:10.1016/j.drudis.2019.09.022

Non-Human Toxicity Excerpts · 2 items

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Renal adenomas developed in rats receiving an injectable gold product similar to Solganal suspension at doses of 2 mg/kg weekly for 46 weeks followed by 6 mg/kg daily for 47 weeks. These doses were higher and administered more frequently than the recommended human doses. The adenomas were similar histologically to those produced by chronic administration of other gold compounds and heavy metals such as lead or nickel. Renal tubular cell neoplasia consisting of renal adenoma and adenocarcinoma were noted in dose-response relationship in another study in rats using daily intramuscular doses of 3 mg/kg and 6 mg/kg for up to 2-years. These doses were higher and administered more frequently than the recommended human doses. In this same study, sarcomas at the injection site occurred in some rats but their numbers were not sufficient to demonstrate a dose-response relationship.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Myochrysine /aurothioglucose/ has been shown to be teratogenic during the organogenetic period of in rats and rabbits Hydrocephaly and microphthalmia were malformation observed in rats when myochrysine was administered subcutaneously at a dose of 25 mg/kg/day from day 6 through day 15 of gestation. In rabbits, limb malformations and gastroschisis were the malformations observed when myochrysine was administered subcutaneously at doses 20 to 45 mg/kg/day from day 6 through day 18 of gestation.

Antidote and Emergency Treatment · 5 items

In the event of toxic reactions gold therapy should be discontinued immediately. In the presents of mild reactions, it may be sufficient to discontinue the administration of Solganal /aurothioglucose/ suspension for a short period and then to resume treatment with smaller doses.

Dermatitis and pruritus may respond to soothing lotions, other appropriate antipruritic treatment or topical glucocorticoids.

If dermatitis or stomatitis becomes severe or spreads, systemic glucocorticoid treatment may be indicated. For renal hematologic, and most other adverse reactions, glucocorticoids may be required in larger doses and for longer time than dermatologic reactions. Often this treatment may be required for many months because of the slow elimination of gold from the body.

If severe adverse reactions do not improve with steroid treatment in patients who receive large doses of gold, a chelating agent, such as dimercaprol (BAL), may be used. In one case it was reported that penicillamine was beneficial in the treatment of gold-induced thrombocytopenia. Adjunctive use of an anabolic steroid with other drugs (i.e., BAL, penicillamine, and corticosteroids) may contribute to recovery of bone marrow deficiency.

For more Antidote and Emergency Treatment (Complete) data for AUROTHIOGLUCOSE (7 total), please visit the HSDB record page.

Safety data

PPE
dust mask type N95 (US), Eyeshields, Faceshields, Gloves
wgk
3
ridadr
2811
hs_code
2843300000
Toxicity
LD50 intravenous in chicken: 1gm/kg
risk_code
42/43
Signal word
Warning
Symbol(GHS)
GHS07
hazard_code
Xn
safety_code
22-36/37-45
hazard_class
6.1(b)
Storage Class
11 - Combustible Solids
packing_group
III
Hazard statements
H317-H412
Hazard Classifications
Resp. Sens. 1Skin Sens. 1
Precautionary statements
P261-P272-P273-P280-P302+P352-P333+P313
Hazardous Substances Data
12192-57-3(Hazardous Substances Data)

The effects of aurothioglucose, on basal and forskolin-activated adenylyl cyclase activity in human total lymphocyte membranes and in membranes of T and B lymphocyte subsets /was studied/. The gold compounds inhibited adenylyl cyclase activity. This inhibitory effect required the presence of both the sulfhydryl ligands and aurous cation. Regulation of lymphocyte adenylyl cyclase by gold compounds represents a potential mode of action of these drugs in rheumatic disease.

Transcription factor NF-kappaB controls the expression of a number of genes including those for cell adhesion molecules such as E-selectin, ICAM- 1 and VCAM- 1. These cell adhesion molecules are known to play important roles in a critical step of tumor metastasis; the arrest of tumor cells on the venous or capillary bed of the target organ. NF-kappaB is activated by extracellular signals such as those elicited by the proinflammatory cytokines, TNF and IL-1. The adhesion of tumor cells to IL-1 beta-treated HUVEC /human umbilical vein endothelial cells/ was inhibited by gold compounds such as aurothioglucose.

Biological Half-Life · 2 items

The biological half-life of gold salts (like aurothioglucose) following a single 50 mg dose demonstrates a biological half-life of about 3-27 days, where the half-life seemingly increases with increased number of doses. Following successive weekly doses, the half-life increases and may become 14-40 days after the third dose and up to 168 days after the eleventh weekly dose.

The biological half-life of gold salts following a single 50 mg dose has been reported to range from 3 to 27 days. Following successive weekly doses, the half-life increases and may be 14 to 40 days after the third dose and up to 168 days after the eleventh weekly dose.

Metabolism/Metabolites · 2 items

Although the exact metabolic fate of aurothioglucose is not formally understood, the principal gold species that can be found in the urine and blood of a patient following the administration of the drug is [Au(CN)2]-.

For a patient receiving gold sodium thiomalate the principal gold species in the urine is [Au(CN)2]-, which is also seen in a low molecular weight infiltrate of the blood. The same compound is also identified in the urine and blood of a patient taking solganol

MeSH Pharmacological ClassificationDrugs that are used to treat RHEUMATOID ARTHRITIS.
Absorption, Distribution and Excretion · 6 items

In general, aurothioglucose is administered via intramuscular injection - preferably intragluteally - after which the resultant absorption is typically slow and erratic. Gold is absorbed from injection sites, reaching peak concentration in blood in about 4 to 6 hours. After a single intramuscular injection of 50 mg of aurothioglucose suspension in two subjects, peak serum levels were observed at approximately 235 g/dL and 450 g/dL. Storage of gold in human tissues depends upon organ mass as well as the concentration of gold.Subsequently, tissues having the highest gold levels (w/w) may not necessarily have the largest total amounts of gold. The highest concentrations of gold are generally found in the lymph nodes, adrenal glands, liver, kidneys, bone marrow, and spleen. Relatively small concentrations are actually found in the articular structures. In particular, following the administration of aurothioglucose doses, about 85% of the resultant plasma gold will be stored in the major bodily gold depots, which in decreasing order of total gold content are, the lymph nodes, bone marrow, liver, skin, and bone.

Following a single intramuscular injection of 50 mg aurothioglucose in each of two patients, one study determined that approximately 70% of the agent is eliminated in the urine and 30% in the faeces. In general, excretion is primarily in the urine.

Readily accessible data regarding the volume of distribution of aurothioglucose is not available.

When a standard weekly treatment schedule of aurothioglucose administrations is followed, about 40% of the given dose is excreted each week, while the remainder is excreted over a longer period.

The true potential of gold compounds, including ... aurothioglucose, to cumumulate has not been clearly defined, but it is clear that substantially larger amounts of gold are retained in the body during therapy with parenteral gold compounds than during therapy with auranofin.

Small amounts of gold have been shown to be distributed into milk in women receiving aurothioglucose ... .

Uses & manufacturing

Uses · 2 items

MEDICATION

To produce obesity in experimental animals.

Methods of ManufacturingGold thioglucose is prepared by adding a solution of gold bromide to an aqueous solution of thioglucose that contains sulfur dioxide. After heating, the product is precipitated by the addition of ethanol.
Formulations/PreparationsParenteral: Suspension, sterile, for IM use only, 50 mg/ml; Solganal (with aluminum monosterate 2% and propylparaben 0.1% in sesame oil), Schering
Applications · 4 items

DescriptionAurothioglucose is highly water soluble, and its aqueous solutions decompose on long standing. It therefore is available as a suspension in sesame oil. Gold content is approximately 50%. Following IM injection, it is highly protein bound (95%), and peak plasma levels are achieved within 2 to 6 hours. Following a single 50-mg dose, the biological half-life ranges from 3 to 27 days, but following successive weekly doses, the half-life increases to 14 to 40 days after the third dose. The therapeutic effect does not correlate with serum plasma gold levels but appears to depend on total accumulated gold. Aurothioglucose is indicated for the adjunctive treatment of adult and juvenile rheumatoid arthritis.

HistoryIn 1927, aurothioglucose was found to relieve joint pain when used to treat bacterial endocarditis. The area of chrysotherapy had begun. Subsequent investigations led to an extensive study of gold compounds in Great Britain by the Empire Rheumatism Council, which reported in 1961 that sodium aurothiomalate was effective in slowing the development of progressive joint diseases. Both aurothioglucose and sodium aurothiomalate are orally ineffective and are administered by IM injection. In 1985, the first orally effective gold compound for arthritis, auranofin, was introduced in the United States. Several other gold compounds have been evaluated clinically but do not appear to offer advantages in terms of efficacy or toxicity.

UsesAurothioglucose hydrate has been used in redox stress survival assay in human cell lines and for inducing obese phenotype in mice.

UsesTo produce obesity in experimental animals.

Suppliers41 total

国药集团化学试剂有限公司86-21-63210123 · [email protected]
上海康朗生物科技有限公司021-61998208 18217752821 · [email protected]
上海钰博生物科技有限公司021-60514606 18321282235 · [email protected]
艾吉析科技(上海)有限公司17717235263 · [email protected]
Aladdin Scientific[email protected]
怀化市冰峰化工有限公司0745-2866851 17711757908 · [email protected]
杭州璟皓生物科技有限公司(原河南辛迪加生物)17513242016 · [email protected]
MedChemexpress LLC021-58955995 · [email protected]
江苏艾康生物医药研发有限公司025-66028182 17714375163 · [email protected]
Sigma-Aldrich西格玛奥德里奇(上海)贸易有限公司021-61415566 800-8193336 · [email protected]
AN PharmaTech Co Ltd86(21)68097365 · [email protected]
上海陶术生物科技股份有限公司+1-781-999-5354; +1-00000000000 · [email protected]
BOC Sciences16314854226; +8616314854226 · [email protected]
HANGZHOU LEAP CHEM CO., LTD.+86-571-87711850 +86-15355479329 · [email protected]
安耐吉化学&3A(安徽泽升科技股份有限公司)400-0056266 · [email protected]
风咏生物(AbMole)021-10000000 13000000000 · [email protected]
BOC Sciences16314854226 · [email protected]
上海颖心实验室设备有限公司021-021-59178156 15300768757 · [email protected]
山东西亚化学有限公司4009903999 13395398332 · [email protected]
Cckinase, Inc.+1 (732)236-3202 · [email protected]
山东小野化学股份有限公司0539-6362799 20)
Watson Biotechnology Co.,Ltd+86-18186686046 · [email protected]
Shanghai Acmec Biochemical Technology Co., Ltd.+86-18621343501 · [email protected]
Musechem+1-800-259-7612 · [email protected]
河南天孚化工有限公司+86-0371-55170693 +86-19937530512 · [email protected]
career henan chemical co+86-0371-86658258 · [email protected]
上海吉至生化科技有限公司021-4009004166/18616739031 18616739031 · [email protected]
深圳聚合生化科技有限公司+86-400-002-6226 13028896684 · [email protected]
湖北摆渡化学有限公司027-59106051 13627137652 · [email protected]
上海沪震实业有限公司021-60345367 13916550749 · [email protected]
上海迈瑞尔生化科技有限公司18621169109 · [email protected]
SHANGHAI KEAN TECHNOLOGY CO., LTD.+8613817748580 · [email protected]
ChemeGen 中国18818260767 · [email protected]
重庆卡兰医药有限公司[email protected]
北京百灵威科技有限公司18210857532 18210857532 · [email protected]
DAYANG CHEM (HANGZHOU) CO.,LTD+86-88938639 +86-17705817739 · [email protected]
上海联迈生物工程有限公司021-67680335 13052188602 · [email protected]
上海雅吉生物科技有限公司021-34661275 15301693058 · [email protected]
上海鼓臣生物技术有限公司021-34675735 19147740836 · [email protected]
DONBOO AMINO ACID COMPANY13063595538 · [email protected]
湖北清北云研医药科技有限责任公司18162595016; 18162595016 · [email protected]