Sodium aurothiomalate   中文名称: 金硫丁二钠

在所有研究的细胞系（A549、H1437、H2170、H460、H510、H187、H1703 和 A427 肺）壁生长剂量依赖性肽系统中，金硫苹果酸钠（0.001、0.01、0.1、1、10、100 和 1000 μM） ) 导致附着独立性，IC50 范围为 300 nM 至 107 μM。肺腺癌(LAC)和小细胞肺癌(SCLC)细胞对金硫甲醛表现出强烈的敏感性[1]。此外，用于肺腺癌的金硫苹果酸钠（25 μM；6 小时）可阻断 TNFa 诱导的 NF-kB 激活，并且 NF-kB 激活促炎基因（例如 E-选择素和环氧合酶-2）。通过与 PKCγ 结合并阻止 PKCι-Par6-Rac1-Pak-Mek 1,2-Erk 1,2 信号放大器的激活，金硫苹果 DNA 抑制非小细胞肺癌 (NSCLC) 的生长 [3]。在不影响肿瘤细胞停滞或血管发育的情况下，硫代苹果酸钠可抑制体内 Mek/Erk 信号传导并降低缺血指数 [1]。

金硫苹果酸钠（2、6、20 或 60 mg/kg/天；皮内注射；40 天）在 A427 细胞肿瘤中测试的所有浓度下均表现出统计学上显着的肿瘤生长抑制作用，使用金硫苹果酸钠（20、60 mg/kg）的 A427 细胞/天；皮内注射；15 天）仅在 60 mg/kg 剂量下，H460 肿瘤中显示出统计学上显着的反应（肿瘤尺寸减小约 50%），因为 H460 细胞对毒性有反应 [1]。金硫苹果酸钠（60 mg/kg/天；腹腔注射；持续六周）在三周大的 KrasLA2 小鼠中表现出肿瘤生长减少。硫代苹果酸钠在体内中止 Kras 介导的黄昏肺肿瘤肺泡干细胞 (BASC) 的互补和肺部生长 [2]。

蛋白质印迹分析 [1]
细胞类型：牛动脉内皮细胞 (BAEC)
测试浓度：25 uM 1]。
孵育持续时间：6小时
实验结果：以剂量依赖性方式抑制TNFa诱导的NF-kB依赖性基因表达方式。不影响 COS7 细胞中 TrxR1 mRNA 水平。

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.

---

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

---

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.

---

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.

---

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

---

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

105.56

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

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

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

配方 1 中的溶解度: 50 mg/mL (Infinity mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。