In all investigated cell lines (A549, H1437, H2170, H460, H510, H187, H1703, and A427 lung) wall growth dose-dependent peptide system, sodium aurothiomalate (0.001, 0.01, 0.1, 1, 10, 100, and 1000 μM) causes attachment-independence with an IC50 ranging from 300 nM to 107 μM. The cells of lung adenocarcinoma (LAC) and small cell lung cancer (SCLC) exhibit a strong sensitivity to aurothiomaldehyde [1]. Additionally, aurothiomalate sodium (25 μM; 6 hours) used in lung adenocarcinoma blocks TNFa-induced NF-kB activation, and NF-kB activates pro-inflammatory genes (e.g., E-selectin and cyclooxygenase-2). By binding to PKCγ and preventing the activation of PKCι-Par6-Rac1-Pak-Mek 1,2-Erk 1,2 signal amplifier, golden sulfur apple DNA suppresses the growth of non-small cell lung cancer (NSCLC) [3]. Without impacting tumor cell arrest or blood vessel development, sodium thiomalate inhibits Mek/Erk signaling in vivo and lowers the ischemia index [1].

Sodium aurothiomalate (2, 6, 20, or 60 mg/kg/day; intradermal injection; 40 days) demonstrated statistically significant tumor growth inhibition at all concentrations tested in A427 cell tumors, A427 cells with sodium aurothiomalate (20, 60 mg/kg/day; intradermal injection; 15 days) showed a statistically significant response in H460 tumors only at the 60 mg/kg dose (tumor size reduction of approx. 50%), as H460 cells respond to toxicity [1]. Sodium aurothiomalate (60 mg/kg/day; i.p.; for six weeks) exhibited decreased tumor growth in three-week-old KrasLA2 mice. Sodium thiomalate in vivo suspends Kras-mediated complementation and lung growth of dusk lung tumor alveolar stem cells (BASCs) [2].

Western Blot analysis [1]
Cell Types: Bovine arterial endothelial cells (BAEC)
Tested Concentrations: 25 uM 1].
Incubation Duration: 6 hrs (hours)
Experimental Results: Inhibited TNFa-induced NF-kB-dependent gene expression in a dose-dependent manner. Does not affect TrxR1 mRNA levels in COS7 cells.

Animal/Disease Models: 4-6 weeks old female nude mice A427 or H460 cells [1]
Doses: 2, 6, 20 or 60mg/kg
Route of Administration: intramuscularinjection; daily; 40-day
Experimental Results: Tested in A427 cell tumors Statistically significant tumor growth inhibition was demonstrated at all concentrations, as A427 cells were highly reactive.

Absorption, Distribution and Excretion
Gold sodium thiomalate solutions are rapidly absorbed following IM injection, with peak serum concentrations occurring in 3-6 hours.
The major route of elimination of an IV dose of gold sodium thiomalate is urinary excretion, with a mean of 35% of the dose found in the urine in ten days. Fecal elimination accounts for an additional 9.4% of the IV dose excreted in ten days, probably as a result of biliary secretion.
The apparent volume of distribution is 0.26 +/- 0.051 kg-1
7.0 ml/ kg/day
Higher tissue levels occur with parenteral gold salts, with a mean steady state plasma level of 1 to 5 ug/ml. Drug is distributed widely throughout the body in lymph nodes, bone marrow, kidneys, liver, spleen, and tissues. About 85% to 90% is protein-bound.
Gold has been shown to cross the placenta in pregnant women receiving gold sodium thiomalate. Small amounts of gold have been shown to be distributed into milk in women receiving ... gold sodium thiomalate.
Gold sodium thiomalate solutions are rapidly absorbed following IM injection, with peak serum concentrations occurring in 3-6 hours.
Following single 10-mg doses of gold sodium thiomalate, serum gold concentrations showed a biphasic decline with a relatively rapid early phase (serum half-life about 43 hours) and a slow late phase (serum half-life about 6 days). The slow phase of decline may result from excretion and the rapid phase of decline may result from tissue distribution. The true potential of gold compounds, including ... gold sodium thiomalate, to cumulate 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.
For more Absorption, Distribution and Excretion (Complete) data for GOLD SODIUM THIOMALATE (8 total), please visit the HSDB record page.

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Metabolism / Metabolites
No data available.
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

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Biological Half-Life
12.5 days
Following single 10-mg doses of gold sodium thiomalate, serum gold concentrations showed a biphasic decline with a relatively rapid early phase (serum half-life about 43 hours) and a slow late phase (serum half-life about 6 days).
...Terminal log-linear phases corresponded to a mean disposition half-life of 25 days...
... the mean alpha half-lives were 0.738 and 1.78 hr for the iv and im routes, respectively. The corresponding terminal (beta) half-lives were 54.1 and 63.0 hr...
Four normal male volunteers participated in a study designed to examine the disposition of gold given intramuscularly as gold sodium thiomalate. Blood samples were collected for 32 days following the administration of 10 mg of gold sodium thiomalate. .... Terminal log-linear phases corresponded to a mean disposition half-life of 25 days. ...

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Excretion of gold into milk after gold sodium thiomalate has not been rigorously studied. Case reports indicate that gold appears in milk in small quantities and at least a little of it is absorbed because it is detectable in the infant's urine. No convincing cases of toxicity have been reported. Monitoring for possible adverse effects in the breastfed infant would seem prudent. Opinions of authors of review articles vary from recommending avoidance to allowing use. Since gold salts are rarely used any longer, an alternative is preferred.
◉ Effects in Breastfed Infants
Four infants reportedly have been breastfed during maternal gold therapy (including gold sodium thiomalate and gold aurothioglucose). Transient facial edema occurred in an 18-month-old infant, 3 months after the mother's treatment stopped. The reaction was possibly due to gold in the mother's milk ingested by the infant.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
About 85-90% of the drug is protein bound.

[1]. Atypical protein kinase C iota expression and aurothiomalate sensitivity in human lung cancer cells. Cancer Res. 2008 Jul 15;68(14):5888-95.

[2]. Atypical protein kinase C{iota} is required for bronchioalveolar stem cell expansion and lung tumorigenesis. Cancer Res. 2009 Oct 1;69(19):7603-11.

[3]. Overexpression of thioredoxin reductase 1 regulates NF-kappa B activation. J Cell Physiol. 2004 Jan;198(1):22-30.

Disodium aurothiomalate is an organic sodium salt which is the disodium salt of gold thiomalic acid, with a basic unit comprising two sodium cations and a divalent aurothiomalate anion. It contains an aurothiomalate(2-).
Sodium aurothiomalate is a gold compound that is used for its immunosuppressive anti-rheumatic effects. Gold Sodium Thiomalate is supplied as a solution for intramuscular injection containing 50 mg of Gold Sodium Thiomalate per mL. It is most effective in active progressive rheumatoid arthritis and of little or no value in the presence of extensive deformities or in the treatment of other forms of arthritis.
Gold Sodium Thiomalate is the sodium salt of gold thiomalic acid, an organogold compound with antirheumatic and potential antineoplastic activities. Gold sodium thiomalate (GST) appears to inhibit the activity of atypical protein kinase C iota (PKCiota) by forming a cysteinyl-aurothiomalate adduct with the cysteine residue Cys-69 within the PB1 binding domain of PKCiota. This prevents the binding of Par6 (Partitioning defective protein 6) to PKCiota, thereby inhibiting PKCiota-mediated oncogenic signaling, which may result in the inhibition of tumor cell proliferation, the promotion of tumor cell differentiation, and the induction of tumor cell apoptosis. Atypical PKCiota, a serine/threonine kinase overexpressed in numerous cancer cell types, plays an important role in cancer proliferation, invasion, and survival; Par6 is a scaffold protein that facilitates atypical PKC-mediated phosphorylation of cytoplasmic proteins involved in epithelial and neuronal cell polarization.
A variable mixture of the mono- and disodium salts of gold thiomalic acid used mainly for its anti-inflammatory action in the treatment of rheumatoid arthritis. It is most effective in active progressive rheumatoid arthritis and of little or no value in the presence of extensive deformities or in the treatment of other forms of arthritis.

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Drug Indication
A disease-modifying antirheumatic drug (DMARD) indicated for the symptomatic treatment of arthritis.

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Mechanism of Action
The precise mechanism of action is unknown. It is known that sodium aurothiomalate inhibits the synthesis of prostaglandins. The predominant action appears to be a suppressive effect on the synovitis of active rheumatoid disease.
...The effects of aurothiomalate, 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 aurothiomalate.
Gold dermatosis is mediated, at least in part, by allergic mechanisms

C4H3O4S-3.AU+.NA+

367.08602

389.921

12244-57-4

4846-27-9 (free acid);12244-57-4 (sodium);39377-38-3 (sodium hydrate);

22318

Off-white to light yellow solid powder

0

5

1

12

126

0

VXIHRIQNJCRFQX-UHFFFAOYSA-K

InChI=1S/C4H6O4S.Au.2Na/c5-3(6)1-2(9)4(7)8;;;/h2,9H,1H2,(H,5,6)(H,7,8);;;/q;3*+1/p-3

disodium;gold(1+);2-sulfidobutanedioate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

H2O : ~250 mg/mL

Solubility in Formulation 1: 50 mg/mL (Infinity mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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