Sodium aurothiomalate targets atypical protein kinase C iota (PKCι) and thioredoxin reductase (TrxR). It inhibits PKCι activity by forming a cysteinyl-aurothiomalate adduct with Cys-69 within the PB1 binding domain, preventing Par6 binding and inhibiting oncogenic signaling. It also inhibits TrxR1 activity and TNFα-induced NF-κB activation. The compound additionally inhibits prostaglandin synthesis, contributing to its anti-inflammatory effects.

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 inhibits tumor cell growth/proliferation in a dose-dependent manner across multiple lung cancer cell lines (A549, H1437, H2170, H460, H510, H187, H1703, A427) with IC50 values ranging from 300 nM to 107 μM. At 25 μM, it blocks TNFα-induced NF-κB activation and inhibits pro-inflammatory gene expression in lung adenocarcinoma cells. It suppresses NSCLC growth by disrupting the PKCι-Par6-Rac1-Pak-Mek1,2-Erk1,2 signaling pathway. The compound does not induce apoptosis but inhibits proliferation.

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].
In vivo, Sodium aurothiomalate demonstrates significant tumor growth inhibition in A427 cell tumors at doses of 2, 6, 20, and 60 mg/kg/day via intradermal injection over 40 days. In H460 tumors, a 60 mg/kg/day dose reduced tumor size by approximately 50%. In KrasLA2 mice, 60 mg/kg/day intraperitoneal administration for six weeks decreased tumor growth. The compound also inhibits Mek/Erk signaling in vivo and reduces ischemia index without affecting tumor cell arrest or blood vessel development.

In vitro enzyme assays for Sodium aurothiomalate typically involve measuring PKCι activity inhibition. Recombinant PKCι is incubated with varying concentrations of the compound (0.001-1000 μM), and kinase activity is measured using appropriate peptide substrates and ATP. TrxR inhibition assays measure the reduction of insulin or other substrates in the presence of NADPH. IC50 values are determined from dose-response curves. Western blot analysis can be performed to assess inhibition of TNFα-induced NF-κB-dependent gene expression.

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.
In vitro cellular assays for Sodium aurothiomalate involve culturing lung cancer cell lines (A549, H1437, H2170, H460, H510, H187, H1703, A427) in appropriate media. Cells are treated with the compound at concentrations ranging from 0.001 to 1000 μM for specified durations. Cell proliferation is assessed using colony formation assays or MTT assays. IC50 values are calculated from dose-response curves. Western blot analysis can be performed to evaluate inhibition of signaling pathways such as NF-κB and Erk.

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.
In vivo animal studies for Sodium aurothiomalate are conducted in mouse xenograft models using lung cancer cell lines such as A427 and H460. The compound is administered via intradermal injection at doses of 2, 6, 20, or 60 mg/kg/day for 15-40 days. Alternatively, intraperitoneal administration at 60 mg/kg/day for six weeks is used in KrasLA2 transgenic mice. Tumor growth is monitored by measuring tumor size, and statistical significance is determined compared to vehicle controls.

Absorption, Distribution and Excretion
Disodium aurothiomalate solution is rapidly absorbed after intramuscular injection, with peak serum concentrations reached within 3–6 hours. The primary route of excretion after intravenous administration is urinary excretion, with an average of 35% of the dose excreted in the urine over ten days. An additional 9.4% of the intravenously administered dose is excreted in feces, likely due to bile secretion. The apparent volume of distribution is 0.26 ± 0.051 kg⁻¹. The dosage is 7.0 ml/kg/day. Parenteral administration results in higher concentrations of gold salts in tissues, with average steady-state plasma concentrations ranging from 1 to 5 μg/ml. The drug is widely distributed throughout the body, including lymph nodes, bone marrow, kidneys, liver, spleen, and various tissues. Approximately 85% to 90% of the drug is bound to proteins. Studies have shown that gold in pregnant women taking Disodium aurothiomalate can cross the placenta. Small amounts of gold are secreted into the breast milk of pregnant women taking Disodium aurothiomalate.
Absorption of sodium auronide solution is rapid after intramuscular injection, with peak serum concentrations reaching their maximum within 3-6 hours.
Following a single 10 mg injection of sodium auronide, serum gold concentrations exhibit a biphasic decline, with a rapid early decline (serum half-life approximately 43 hours) and a slower late decline (serum half-life approximately 6 days). The slow decline may be due to drug excretion, while the rapid decline may be due to drug distribution in tissues. The true accumulation potential of gold compounds, including sodium auronide, is not yet clear, but it is certain that the amount of gold remaining in the body during treatment with gold compounds administered via the parenteral route is significantly greater than that with aurinolone.
For more complete data on the absorption, distribution, and excretion of sodium auronide (8 types), please visit the HSDB record page.

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Metabolism/Metabolites
No data available.
For patients treated with sodium auronide, the predominant gold species in urine is [Au(CN)2]-, and low molecular weight infiltrates are also observed in the blood.

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Biological Half-Life
12.5 days
After a single dose of 10 mg sodium auronide, serum gold concentrations exhibited a biphasic decline, with a relatively rapid early decline (serum half-life approximately 43 days), followed by a slow late decline (serum half-life approximately 6 days).
...The mean treatment half-life corresponding to the terminal log-linear pathway was 25 days...
...The mean α-half-lives for intravenous and intramuscular administration were 0.738 hours and 1.78 hours, respectively. The corresponding terminal (β) half-lives were 54.1 hours and 63.0 hours, respectively...
A study involving four healthy male volunteers investigated the treatment of gold following intramuscular injection of sodium auronide. Blood samples were collected for 32 consecutive days following the injection of 10 mg sodium auronide. ...The mean treatment half-life corresponding to the terminal log-linear pathway was 25 days. ...
Sodium aurothiomalate is administered intramuscularly as a solution containing 50 mg/mL. The compound has a molecular weight of 390.08 g/mol. It is supplied as a powder with ≥98% purity and is soluble in appropriate solvents. Detailed pharmacokinetic parameters such as half-life, volume of distribution, and clearance are not extensively documented in publicly available sources. The compound is intended for research use only and not for human therapeutic applications.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
There has been no rigorous research on the excretion of gold into breast milk after administration of Disodium aurothiomalate. Case reports indicate that small amounts of gold are present in breast milk, and at least a small amount is absorbed, as gold can be detected in infant urine. There are currently no conclusive reports of toxicity. Monitoring breastfed infants for potential adverse reactions appears to be a prudent practice. Authors of review articles have differing opinions, with some advising against use and others recommending its permissibility. Since gold salts are now rarely used, alternatives are preferable.
◉ Effects on Breastfed Infants
Four infants have been reported to have been breastfed while their mothers were receiving gold therapy (including Disodium aurothiomalate and glucosinolate). One 18-month-old infant developed transient facial edema three months after the mother stopped treatment. This reaction was likely due to the infant ingesting gold from breast milk.
◉ Effects on Lactation and Breast Milk
No relevant published information was found as of the revision date.

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Protein binding
Approximately 85-90% of drugs bind to proteins.

Sodium aurothiomalate is generally well-tolerated at therapeutic doses but can cause side effects typical of gold therapy, including skin reactions, stomatitis, and proteinuria. It is contraindicated in patients with severe renal or hepatic impairment. The compound has been used clinically as a DMARD for rheumatoid arthritis but is now primarily a research tool. Standard laboratory safety precautions should be taken when handling the compound.

[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 organosodium salt, the disodium salt of gold thiomalate, whose basic unit consists of two sodium ions and a divalent gold thiomalate anion. It contains the gold (2-) ion. Disodium aurothiomalate is a gold compound used for its immunosuppressive and antirheumatic effects. It is supplied as an intramuscular solution containing 50 mg of Disodium aurothiomalate per milliliter. It is most effective against active progressive rheumatoid arthritis, but has little or no effect on cases with extensive deformities or for the treatment of other types of arthritis. Disodium aurothiomalate is the sodium salt of gold thiomalate, an organogold compound with antirheumatic and potential antitumor activity. Gold-thiomalate (GST) appears to inhibit PKC iota activity by forming a cysteine-gold-thiomalate adduct with the cysteine residue Cys-69 within the PB1 binding domain of the atypical protein kinase C iota (PKC iota). This prevents Par6 (separation defect protein 6) from binding to PKC iota, thereby inhibiting PKC iota-mediated oncogenic signaling, which may lead to inhibition of tumor cell proliferation, promotion of tumor cell differentiation, and induction of tumor cell apoptosis. Atypical PKC iota is a serine/threonine kinase overexpressed in various cancer cell types and plays an important role in cancer proliferation, invasion, and survival. Par6 is a scaffold protein that promotes atypical PKC-mediated phosphorylation of cytoplasmic proteins involved in the polarization of epithelial cells and neurons. Gold-thiomalate sodium is a mixture of monosodium and disodium salts of gold-thiomalate, primarily used to treat rheumatoid arthritis, exerting its anti-inflammatory effects. It is most effective for active progressive rheumatoid arthritis, but has little or no effect on cases with extensive deformities or for the treatment of other types of arthritis.

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

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Mechanism of Action
Its exact mechanism of action is unclear. Disodium aurothiomalate is known to inhibit prostaglandin synthesis. Its primary effect appears to be inhibition of active rheumatoid synovitis.
...The effects of gold thiomalate on basal adenylate cyclase activity and fossiclin-activated adenylate cyclase activity in the membranes of human total lymphocytes and T-cell and B-cell subsets were investigated. Gold compounds inhibit adenylate cyclase activity. This inhibition requires 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 responsible for 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., gold thiomalate) can inhibit the adhesion of tumor cells to IL-1β-treated HUVECs (human umbilical vein endothelial cells). Chloroderma is at least partially mediated by an allergic mechanism.
Sodium aurothiomalate is a gold-containing compound that has been used for decades as a disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis. It is a potent and specific inhibitor of oncogenic PKCι signaling and a potent TrxR inhibitor. The compound is also known as gold sodium thiomalate and is supplied as a solution for intramuscular injection. It is not approved for human therapeutic use in many jurisdictions and is available only for research purposes.

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.)