Although auranofin is a medication that has been approved to treat rheumatoid arthritis, it is also being researched for possible therapeutic uses in cancer and maybe neurodegeneration. Cells are induced by auranofin via the Bax/Bak induction pathway. In SKOV3 cells, auranofin inhibits the cell division and rapid death in a dose- and time-dependent manner. Treatment with auranofin can decrease the expression of anti-solvent Bcl-2 in SKOV3 cells, raise the protein levels of apoptosis-inducing proteins Bax and Bim, and stimulate ischemia caspase-3 [2]. The lipophilic gold compound auranofin has immunosuppressive and anti-inflammatory properties. Following auranofin treatment, auranofin stain PC3 human significantly regulates cell growth activity, with an IC50 value of 2.5 μM after 24 hours [3].

Reduced paw edema markers, full restoration of suppressed IL-2 production, and decreased elevation of IL-1 production were the outcomes of auranofin-treated zodiac arthritic markers as a preventive measure[4]. However, there was no response to suppressed IL-3 production.

Absorption, Distribution and Excretion
Approximately 60% of the absorbed gold (15% of the administered dose) from a single dose of auranofin is excreted in urine; the remainder is excreted in the feces.
In vivo, gold from auranofin is approximately 60% bound to serum proteins. Of the gold bound to serum proteins, 82% is bound to albumin and the remainder to alpha1-, alpha2-, and beta-globulins and possibly to IgG. Less than 1-2% of gold from auranofin in serum is present as free gold; serum concentrations of free gold attained with auranofin appear to be similar to those attained with gold sodium thiomalate.
Following oral administration of multiple doses of auranofin in animals, gold is distributed in highest concentrations into the kidneys; gold is also distributed into the spleen, lungs, adrenals, and liver, with lower concentrations being distributed into the heart, testes, GI tract, muscle, eyes, fat, and brain. In animals (and possibly in humans), small amounts of gold from auranofin are distributed into bile. Synovial fluid gold concentrations in rheumatoid arthritis patients receiving auranofin are much lower than those in patients receiving therapy with parenteral gold compounds, but the ratio of blood-to-synovial fluid gold concentrations during auranofin therapy is similar to that during parenteral gold therapy (approximately 1.7:1). Preliminary data suggest that little or no gold cumulates in skin during auranofin therapy, in contrast to the accumulation that occurs during therapy with parenteral gold compounds. Little or no gold accumulation occurs in hair or nails during auranofin therapy, and accumulation of gold in the cornea or lens during therapy with the drug has not been detected to date with total cumulative doses as high as 6.1 g.
Following oral administration of a single 6-mg dose of auranofin in healthy adults, mean peak blood gold concentrations of 0.025 ug/mL (range: 0.014-0.046 ug/mL) occurred at 2 hours. Following oral administration of multiple doses of the drug in patients with rheumatoid arthritis, steady-state blood gold concentrations are usually attained after 8-12 weeks, although periods of 13-16 weeks may be necessary in some patients. While there appears to be considerable interindividual variation, once steady-state blood gold concentrations are attained during auranofin therapy, there appears to be minimal intraindividual variation in blood gold concentration with continued dosing.
Results of animal studies indicate that the ligands of auranofin are almost completely absorbed; since a much smaller fraction of the gold is absorbed, the drug is believed to undergo extensive disruption at its coordination bonds within the GI tract. Some experimental data suggest that auranofin is loosely and reversibly adsorbed onto GI mucosa. Other experimental data suggest that gold-containing forms of auranofin may undergo transmucosal absorption, possibly with the initial metabolic process being deacetylation within the GI mucosa.
For more Absorption, Distribution and Excretion (Complete) data for AURANOFIN (9 total), please visit the HSDB record page.

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Metabolism / Metabolites
Metabolized so rapidly that the intact molecule has not been detected in blood.
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 auranofin
Auranofin, 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranosato-S-(triethylphosphine)- gold(I), ...metabolized in contact with hamster or rat gut wall to yield the deacetylated form of the drug. This product, 1-thio-beta-D-glucopyranosato-S-(triethylphosphine)-gold(I), passed through hamster or rat intestinal wall in an everted gut experiment...
The efflux of gold from red blood cells (RBCs) exposed to 10-100 microM auranofin, triethylphosphine(2,3,4,6-tetra-O-acetyl- 1-beta-D-gludopyranosato-S-)gold(I) was studied. RBCs in whole blood were allowed to accumulate gold, and then were place in fresh plasma or buffered saline solution. ...[14C]Glutathione, generated by in situ labeling, also effluxed and associated with the albumin and gold, providing the first direct evidence that the albumin-gold-glutathione complex (AlbSAuSG) may be a circulating metabolite of auranofin formed after both of the original ligands of auranofin are displaced.

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Biological Half-Life
The mean terminal plasma half-life of auranofin gold at steady state was 26 days (range 21 to 31 days; n = 5). The mean terminal body half-life was 80 days (range 42 to 128; n= 5)
In patients with rheumatoid arthritis receiving an auranofin dosage of 6 mg daily, the terminal plasma and biologic half-lives of gold following the initial dose of the drug averaged 17 days (range: 11-23 days) and 58 days (range: 30-78 days), respectively; after 6 months of therapy with the same dosage, the terminal plasma and biologic gold half-lives averaged 26 days (range: 21-31 days) and 81 days (range: 42-128 days), respectively. ...

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Excretion of gold into milk after auranofin has not been studied. Case reports with other gold salts 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. Opinions of authors of review articles vary from recommending avoidance to allowing use. Monitoring for possible adverse effects in the breastfed infant would seem prudent.
◉ 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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Interactions
...there may be a higher incidence of penicillamine toxicity in patients who have previously shown toxic reactions. The interval between stopping the gold and starting the penicillamine did not influence incidence of toxicity. The development of a rash during gold treatment does not seem to influence the development of a rash during penicillamine treatment, but patients who have had proteinuria or bone-marrow depression during gold treatment may have an increased likelihood of developing a similar side effect with penicillamine.
In a single-patient report, there is the suggestion that concurrent administration of Ridaura /auranofin/ and phenytoin may have increased phenytoin blood levels.

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Non-Human Toxicity Values
LD50 Rat oral 265 mg/kg
LD50 Mouse oral 310 mg/kg

[1]. The thioredoxin reductase inhibitor auranofin triggers apoptosis through a Bax/Bak-dependent process that involves peroxiredoxin 3 oxidation. Biochem Pharmacol. 2008 Oct 30;76(9):1097-109.

[2]. Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53. Int J Oncol. 2014 Oct;45(4):1691-8.

[3]. Auranofin promotes mitochondrial apoptosis by inducing annexin A5 expression and translocation in human prostate cancer cells. J Toxicol Environ Health A. 2014;77(22-24):1467-76.

[4]. Effect of auranofin treatment on aberrant splenic interleukin production in adjuvant arthritic rats. J Immunol. 1987 Nov 15;139(10):3268-74.

[5]. Metallodrug ranitidine bismuth citrate suppresses SARS-CoV-2 replication and relieves virus-associated pneumonia in Syrian hamsters. Nat Microbiol. 2020 Oct 7.

Therapeutic Uses
Auranofin is indicated in the treatment of adult rheumatoid arthritis and is used in the treatment of (juvenile arthritis /NOT included in US product labeling/). ... Gold compounds may induce remission or suppression of rheumatoid arthritis. In chronic advanced rheumatoid arthritis, they may prevent further damage to affected joints; however, they do not reverse existing damage. /Included in US product labeling/

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Drug Warnings
Auranofin appears to be less toxic and better tolerated than currently available parenteral gold compounds, generally resulting in substantially fewer withdrawals from therapy because of adverse reactions (about 15-20% of patients); however, additional experience is needed to more fully characterize the adverse effect profile of auranofin, particularly with long-term therapy. Auranofin produces more adverse GI effects, including those severe enough to require discontinuance of therapy, than parenteral gold compounds, but fewer and substantially less severe adverse mucocutaneous (and possibly renal) effects than parenteral gold compounds. The overall difference in toxicity-related rates of withdrawal from therapy between auranofin and parenteral gold compounds results principally from the decreased frequency and severity of adverse mucocutaneous effects associated with auranofin. The incidence and severity of other auranofin-induced adverse effects appear to be generally comparable to those of parenteral gold compounds.
The most common adverse effects of auranofin are changes in bowel habits, ranging from more frequent or loose stools to diarrhea, which occur in about 45-50% of patients. Auranofin-induced changes in bowel habits are most likely to occur within the first 3 months of therapy, appear to be dose related, and may be accompanied by abdominal cramping, with the effects often occurring principally within the first several hours after ingestion of a dose. The mechanism of GI toxicity has not been established, but may involve a direct effect of the drug on intestinal water and electrolyte absorption. Auranofin-induced changes in bowel habits may be self-limiting and subside with continued therapy or can generally be managed by dosage reduction or temporary discontinuance of the drug (e.g., for 3-7 days). Changes in bowel habits have also been controlled in some patients by temporary concomitant administration of an antidiarrhea agent (e.g., diphenoxylate hydrochloride), by concomitant administration of an oral iron preparation (in patients with iron deficiency anemia), or by increasing the amount of dietary fiber. Auranofin-induced changes in bowel habits have been severe enough to require discontinuance of the drug in about 4-6% of patients. Some patients, particularly geriatric patients, may consider the changes in bowel habits beneficial.
Abdominal cramping or pain has occurred in about 14% of patients receiving auranofin and required discontinuance in about 1% of patients. Nausea, with or without vomiting, has occurred in about 10% of patients and required discontinuance in about 1% of patients. Other adverse GI effects have occurred in about 13% of patients and required discontinuance in about 1% of patients. Adverse GI effects occurring in 3-9% of patients include anorexia, dyspepsia, and flatulence; those occurring in 1-3% of patients include constipation and dysgeusia; those occurring in less than 1% of patients include GI bleeding, melena, and positive stool for occult blood; and those occurring in less than 0.1% of patients include dysphagia and ulcerative enterocolitis. Enterocolitis accompanied by eosinophilia has been reported. ... Epigastric pain and erosive gastritis have been reported rarely in patients receiving auranofin.
Adverse effects involving the skin and mucous membranes are the second most common adverse reactions of auranofin. Rash has occurred in about 24% of patients receiving the drug and required discontinuance in about 3% of patients, and pruritus has occurred in about 17% of patients and required discontinuance in about 1% of patients. Pruritus often occurs before rash becomes apparent and should be considered a warning signal of an impending cutaneous reaction. Although not reported to date with auranofin, the most severe form of cutaneous reaction reported with parenteral gold compounds is generalized exfoliative dermatitis. Gold-induced dermatitis may be aggravated by exposure to sunlight or an actinic rash may develop. Urticaria has occurred in about 1-3% of patients receiving auranofin, hair loss or alopecia in about 2.5% of patients, and angioedema in less than 0.1% of patients.
For more Drug Warnings (Complete) data for AURANOFIN (13 total), please visit the HSDB record page.

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Pharmacodynamics
Auranofin is a gold salt used in treating inflammatory arthritis. Gold salts are called second-line drugs because they are often considered when the arthritis progresses in spite of antiinflammatory drugs (NSAIDs and corticosteroids).

678.132

34031-32-8

24199313

White to off-white solid powder

425.5ºC at 760mmHg

103 - 105ºC

298ºC

2.792

0

10

12

32

532

0

[Au+].[S-]C1([H])C([H])(C([H])(C([H])(C([H])(C([H])([H])OC(C([H])([H])[H])=O)O1)OC(C([H])([H])[H])=O)OC(C([H])([H])[H])=O)OC(C([H])([H])[H])=O.P(C([H])([H])C([H])([H])[H])(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])[H]

AUJRCFUBUPVWSZ-UHFFFAOYSA-M

InChI=1S/C14H20O9S.C6H15P.Au/c1-6(15)19-5-10-11(20-7(2)16)12(21-8(3)17)13(14(24)23-10)22-9(4)18;1-4-7(5-2)6-3;/h10-14,24H,5H2,1-4H3;4-6H2,1-3H3;/q;;+1/p-1

gold(1+);3,4,5-triacetyloxy-6-(acetyloxymethyl)oxane-2-thiolate;triethylphosphane

SKF-D-39162Auranofin SKF-39162 SKF D 39162 SKFD-39162 SKF 39162NSC 321521, Ridauragold thiolSKFD39162 Ridaura

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)

DMSO : ~50 mg/mL (~73.48 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.67 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.08 mg/mL (3.06 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (3.06 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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