HeLa cell survival is affected by goldthioglucose (0-100 μM, 24-72 h), which suppresses TrxR1 activity in the cytoplasm of the cells [1]. For six hours, goldthioglucose (0–30 μM) had no effect on the cells. Extremely low goldthioglucose (0–20 μM, 24 h) demonstrated remarkable synergy with Ebselen, resulting in the oxidation of Trx1 (thioredoxin 1), the build-up of reactive oxygen species (ROS), and cell death [1]. In OM10.1 and Ach2 cells, goldthioglucose (0-100 μM, 3–12 days) suppresses p24 levels and prevents HIV-1 replication [2]. A dose-dependent cell survival experiment using autioglucose (0-25 μM, 12 days) [1]

In a therapeutically relevant mouse model of ARDS, auurothioglucose (25 mg/kg, ip, single dose) dramatically decreased lung injury and recurrence rates. GSH is necessary for aurothioglucose to have a protective effect[3]. i.p., single-dose, 300 mg/kg gold thioglucose

Cell Viability Assay[1]
Cell Types: HeLa cells
Tested Concentrations: 0, 5, 10, 50, 100 μM
Incubation Duration: 24, 48, 72 h
Experimental Results: Percentage of TrxR activity inhibited by more than 90 in HeLa cells at 100 μM. Even after 72 hrs (hours), cell viability was not affected by ATG treatment at a concentration of 100 μM.

---

Western Blot Analysis[1]
Cell Types: HeLa cells
Tested Concentrations: 0, 5, 10 and 100 μM
Incubation Duration: 24 hrs (hours)
Experimental Results: There was no significant oxidation of Trx1 or Trx2 in HeLa cells.

---

Western Blot Analysis[2]
Cell Types: OM10.1, Ach2 Cell
Tested Concentrations: 0, 4, 10, 25 and 100 μM
Incubation Duration: 3, 6 or 12 days
Experimental Results: Significant inhibition of p24 levels. After 12 days of incubation, the viability of cells treated with 10, 25, and 100 μM Aurothioglucose diminished to 60% of the control.

Animal/Disease Models: Adult male C3H/HeN mice (8-12 weeks, LPS/hyperoxia exposed mice, inflammation/hyperoxia ARDS model) [3]
Doses: 25 mg/kg
Route of Administration: ) Induces hypothalamic scientific research [4]. Intratracheal LPS administration was administered intraperitoneally (ip) (ip) 12 hrs (hrs (hours)) later, and the results of a single dose were: lung injury was Dramatically diminished, lung GCLM expression and GSH levels were increased, and mortality was diminished.

Absorption, Distribution and Excretion
Typically, glucosinolate gold is administered via intramuscular injection—preferably in the gluteal region—and absorption is usually slow and unstable. Gold is absorbed from the injection site, reaching peak plasma concentrations in approximately 4 to 6 hours. In two subjects, after a single intramuscular injection of 50 mg glucosinolate gold suspension, peak serum concentrations were observed to be approximately 235 g/dL and 450 g/dL, respectively. The amount of gold stored in human tissues depends on organ mass and the concentration of gold. Therefore, the tissue with the highest gold content (w/w) does not necessarily have the largest total gold content. The tissues with the highest gold concentrations are typically located in lymph nodes, adrenal glands, liver, kidneys, bone marrow, and spleen. Gold concentrations are relatively low in joint structures. Specifically, after administration of glucosinolate gold, approximately 85% of plasma gold is stored in the body's major gold reservoirs, which, in descending order of total gold content, are: lymph nodes, bone marrow, liver, skin, and bones. A study involving two patients who received a single intramuscular injection of 50 mg glucosinolate found that approximately 70% of the drug was excreted in the urine and 30% in the feces. Generally, the drug is primarily excreted in the urine. Currently, there is no readily available data on the volume of distribution of glucosinolate. If glucosinolate is used according to a standard weekly dosing regimen, approximately 40% of the weekly dose is excreted, with the remainder being excreted over a longer period. The true accumulation potential of gold compounds, including glucosinolate, is not fully understood, but it is certain that the amount of gold remaining in the body after treatment with injectable gold compounds is significantly greater than that after treatment with aurinolone. Studies have shown that small amounts of gold are secreted in the breast milk of women receiving glucosinolate treatment. Gold is absorbed from the injection site and reaches peak plasma concentration within 4 to 6 hours. Following a single intramuscular injection of 50 mg Solganal/gold thioglucose suspension, two patients achieved peak serum concentrations of approximately 235 mcg/dL in one patient and approximately 450 mcg/dL in the other. In plasma, 95% of the gold is bound to albumin. Approximately 70% of the gold is excreted in urine and approximately 30% in feces. With a standard weekly treatment regimen, approximately 40% of the weekly dose is excreted, with the remainder excreted over a longer period.
Serious serum gold concentrations rise rapidly after the first injection and decline over the following week. Peak concentrations in the aqueous formulation are higher than in the oil-based formulation, and the decline is also faster. Weekly administration can maintain a sustained increase in basal concentrations for several months, after which serum concentrations tend to stabilize. Significant inter-individual variability in gold concentrations exists with the standard weekly dose. Extended injection intervals lead to a sustained decline in gold levels, with trace amounts of gold still detectable in serum for several months after discontinuation. The incidence of toxic reactions does not appear to be related to the cumulative amount of gold in the body. For more complete data on the absorption, distribution, and excretion of thioglucosinolates (6 types in total), please visit the HSDB record page. Metabolites/Metabolites While the exact metabolic pathway of thioglucosinolates is not fully understood, the predominant gold ion in the urine and blood of patients after administration is [Au(CN)2]-. In patients receiving sodium gold thiomalate, the predominant gold ion in urine is [Au(CN)2]-, and low molecular weight gold ion infiltration is also observed in the blood. The same compound has also been detected in the urine and blood of patients taking salgano. Biological Half-Life The biological half-life of a single 50 mg dose of a gold salt (such as thioglucosinolate) is approximately 3–27 days, and the half-life appears to increase with increasing dosing frequency. The half-life is further prolonged with continuous weekly dosing, potentially reaching 14–40 days after the third dose and even 168 days after the eleventh weekly dosing. According to reports, the biological half-life of a single 50 mg dose of gold salt is 3 to 27 days. With continuous weekly dosing, the half-life is further prolonged, potentially reaching 14 to 40 days after the third dose, and even up to 168 days after the eleventh weekly dose.

Protein Binding
In plasma, 95-99% of drugs bind to albumin.

[1]. Glutathione and glutaredoxin act as a backup of human thioredoxin reductase 1 to reduce thioredoxin 1 preventing cell death by aurothioglucose. J Biol Chem. 2012 Nov 2;287(45):38210-9.

[2]. Anti-rheumatic compound aurothioglucose inhibits tumor necrosis factor-alpha-induced HIV-1 replication in latently infected OM10.1 and Ach2 cells. Int Immunol. 1999 Feb;11(2):143-50.

[3]. The thioredoxin reductase-1 inhibitor aurothioglucose attenuates lung injury and improves survival in a murine model of acute respiratory distress syndrome. Antioxid Redox Signal. 2014 Jun 10;20(17):2681-91.

[4]. Hypolipidemic effect of pantothenic acid derivatives in mice with hypothalamic obesity induced by aurothioglucose. Exp Toxicol Pathol. 2001 Oct;53(5):393-8.

Gold glucoside (also known as glucosinolate gold) was once used to treat rheumatoid arthritis. Modern research on the therapeutic effects of gold salts began in 1935, primarily aimed at reducing inflammation and slowing disease progression in rheumatoid arthritis patients. Since the 1980s, the use of gold compounds has declined due to numerous side effects, limited efficacy, and slow onset of action. Many (if not most) gold compounds that were once used to treat rheumatoid arthritis have been replaced by various currently more effective disease-modifying antirheumatic drugs (DMARDs), such as methotrexate.
A glucosinolate derivative, formerly used as an antirheumatic drug, was used in experiments to induce obesity in animals.
See also: Glucosinolate gold (note moved here).
Indications
Glucosinolate gold is indicated as adjunctive therapy for early active adult and juvenile rheumatoid arthritis that is not adequately controlled by other anti-inflammatory drugs and conservative treatments (such as salicylates, glucocorticoids, etc.). The efficacy of this gold therapy in cases of chronic, advanced rheumatoid arthritis has not been established. After initiating gold preparation therapy, antirheumatic drugs such as salicylates and other anti-inflammatory medications (including steroids and nonsteroidal anti-inflammatory drugs) can be continued. These medications can be gradually discontinued as symptoms begin to improve.

---

Mechanism of Action
Rheumatoid arthritis is an autoimmune disease in which the patient's immune system mistakenly attacks the linings of various bones and joints. These attacks are promoted by a variety of pro-inflammatory immune cells and factors, such as cytokines, histamine, mast cells, macrophages, monocytes, lymphocytes, and leukocytes. The long-term result of this adverse immune response is chronic inflammation and painful tissue damage. The cause of the immune system dysfunction in rheumatoid arthritis is unclear, and there is currently no cure. Similarly, the mechanism of action of glucosinolates is not fully elucidated. However, some studies have shown that the combination of the thiol ligand and the golden cation present in glucosinolates can inhibit the activity of adenylate cyclase in human lymphocyte membranes and T-cell and B-cell subset membranes. In particular, this inhibition of adenylate cyclase and its various isoenzymes could theoretically limit the cyclase's ability to induce mast cell degranulation and histamine release, enhance respiratory burst effects, stimulate resting macrophage activity, induce and activate phagocytes, and induce neutrophil chemotaxis—all of which are pro-inflammatory effects. This study investigated the effects of gold-thioglucose on basal and fosskin-activated adenylate cyclase activity in the membranes of human total lymphocytes and T-cell and B-cell subsets. The results showed that the gold compound inhibited adenylate cyclase activity. This inhibition required the co-presentation of a thiol ligand and a gold cation. The regulation of lymphocyte adenylate cyclase by gold compounds represents a potential mechanism of action for these drugs in rheumatic diseases. The transcription factor NF-κB controls the expression of many genes, including those of cell adhesion molecules such as E-selectin, ICAM-1, and VCAM-1. These cell adhesion molecules are known to play a crucial role in key steps of tumor metastasis, namely, the retention of tumor cells in the venous or capillary beds of target organs. NF-κB can be activated by extracellular signals, such as those induced by pro-inflammatory cytokines TNF and IL-1. Gold compounds (e.g., glucosinolate) can inhibit the adhesion of tumor cells to IL-1β-treated HUVECs (human umbilical vein endothelial cells).

---

Therapeutic Use
...Glucosinolate...is indicated for the treatment of rheumatoid arthritis in adults or children. ...This drug is commonly used to treat patients who experience persistent or exacerbated disease activity despite conservative treatment (e.g., salicylates, especially aspirin, or other nonsteroidal anti-inflammatory drugs, glucocorticoids, etc.). (Included on the US product label)
Gold compounds are used to treat these rheumatic diseases (e.g., psoriatic arthritis, Felty syndrome). Gold compounds; not included on the US product label /

---

Drug Warnings
Patients intolerant to parabens may be intolerant to injectable glucosinolate because this drug may contain propylparaben. Patients allergic to sesame products may also be allergic to the sesame oil carrier in injectable glucosinolate. Dermatitis is the most common reaction. Itching should be considered a warning sign of an impending skin reaction. Erythema may occur, and occasionally more severe reactions such as macules, vesicular dermatitis, and exfoliative dermatitis may occur, leading to hair loss and nail loss. Golden dermatitis (grayish-blue pigmentation) has been reported, especially in sun-exposed areas. Golden dermatitis may be exacerbated by sunlight exposure or present as actinic rashes. Stomatitis is the second most common adverse reaction. Superficial ulceration of the oral mucosa, tongue margins, and palate, diffuse glossitis, or gingivitis may initially present with a metallic taste. Good oral hygiene is recommended. Inflammation of the upper respiratory tract, pharyngitis, gastritis, colitis, tracheitis, and vaginitis have also been reported. Conjunctivitis is rare. For more complete data on drug warnings for AUROTHIGLUCOSE (11 in total), please visit the HSDB record page.

---

Pharmacodynamics
Following administration, serum gold concentrations rise rapidly but decline over the following week. Peak concentrations in the aqueous formulation are higher than in the oil-based formulation, and the decline is also faster. Regular weekly administration can maintain a sustained increase in baseline levels for several months, after which serum concentrations tend to stabilize. Significant inter-individual variability in gold concentrations may occur after standard weekly dosing. Extended injection intervals lead to a sustained decline in gold levels, with trace amounts of gold still detectable in serum for several months after discontinuation. The incidence of toxic reactions appears to be unrelated to plasma gold levels but may be more related to the total cumulative amount of gold in the body.

C6H11AUO5S.XH2O

392.1756

391.999

12192-57-3

12192-57-3 (anhydrous);

454937

White to yellow solid powder

4

6

1

13

160

4

C([C@@H]1[C@H]([C@@H]([C@H](C(O1)[S-])O)O)O)O.[Au+]

XHVAWZZCDCWGBK-BMZZJELJSA-M

InChI=1S/C6H12O5S.Au/c7-1-2-3(8)4(9)5(10)6(12)11-2;/h2-10,12H,1H2;/q;+1/p-1/t2-,3-,4+,5-,6?;/m1./s1

gold(1+);(3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxane-2-thiolate

Aurothioglucose SKF 10056 Solganal

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~125 mg/mL (~318.73 mM)
DMSO : ~6 mg/mL (~15.30 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)