Auranofin
Identification
- Summary
Auranofin is an antirheumatic used to treat active, progressive, or destructive forms of inflammatory arthritis.
- Brand Names
- Ridaura
- Generic Name
- Auranofin
- DrugBank Accession Number
- DB00995
- Background
Auranofin is a gold salt that is capable of eliciting pharmacologic actions that suppress inflammation and stimulate cell-mediated immunity. It has subsequently been listed by the World Health Organization as a member of the antirheumatic agent category. Auranofin appears to induce heme oxygenase 1 (HO-1) mRNA. Heme oxygenase 1 is an inducible heme-degrading enzyme with anti-inflammatory properties.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Auranofin (DB00995)
- Weight
- Average: 678.484
Monoisotopic: 678.132666497 - Chemical Formula
- C20H34AuO9PS
- Synonyms
- (1-Thio-beta-D-glucopyranosato)(triethylphosphine)gold 2,3,4,6-tetraacetate
- 2,3,4,6-Tetra-O-acetyl-1-thio-beta-D-glucopyranosato-S (triethylphosphine)gold
- Auranofin
- Auranofina
- Auranofine
- Auranofinum
- Triethylphosphine gold
- External IDs
- SK&F 39162
- SK&F-39162
Pharmacology
- Indication
Used in the treatment of active, progressive or destructive forms of inflammatory arthritis, such as adult rheumatoid arthritis.
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- Contraindications & Blackbox Warnings
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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).
- Mechanism of action
Inflammatory arthritis can cause joint swelling, warmth, pain, and tenderness; one cause of this condition is rheumatoid arthritis.13 In patients with rheumatoid arthritis, gold salts such as auranofin can be administered to decrease joint inflammation and prevent the destruction of bones and cartilage. Though the mechanism of action of auranofin is not fully established in rheumatoid arthritis, this drug has been shown to inhibit phagocytosis and the release of antibodies and enzymes that play a role in cytotoxic reactions, suppressing the inflammatory response.8,12
Aside from its probable immune effects in inflammatory arthritis, studies have shown that auranofin inhibits thioredoxin reductase. This enzyme has various roles in cell homeostasis, including the regulation of free radicals.8,10 Thioredoxin reductase can be over expressed in various types of tumours, rendering it an attractive target for anticancer drug development.11 Studies have shown that inhibiting thioredoxin reductase can cause oxidative stress and apoptosis of tumour cells by increasing the formation of free radicals. Aurofin's thiol ligand binds with high affinity to thiol and selenol groups, forming irreversible reaction products.8 One study showed that treatment with auranofin increased the production or reactive oxygen species and caused elevation of intracellular calcium concentration in platelets, leading to cell death.11 Another study showed that auranofin enhanced the production of free radicals, governing T-cell activation.9
Target Actions Organism APeroxiredoxin-5, mitochondrial inhibitorHumans AInhibitor of nuclear factor kappa-B kinase subunit beta inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
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.
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Oral, rat: LD50 = > 2000 mg/kg. Symptoms of overdose may include diarrhoea, vomiting, abdominal cramps, and symptoms of hypersensitivity (such as skin rash, hives, itching, and difficulty breathing).
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Auranofin may decrease the excretion rate of Abacavir which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Auranofin which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Auranofin which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Auranofin which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Auranofin which could result in a lower serum level and potentially a reduction in efficacy. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Auranofin which could result in a higher serum level. Aclidinium Auranofin may decrease the excretion rate of Aclidinium which could result in a higher serum level. Acrivastine Auranofin may decrease the excretion rate of Acrivastine which could result in a higher serum level. Acyclovir Acyclovir may decrease the excretion rate of Auranofin which could result in a higher serum level. Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Auranofin which could result in a higher serum level. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- Take with food. Food reduces irritation.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ridaura Capsule 3 mg/1 Oral Sebela Pharmaceuticals Inc. 2016-12-15 Not applicable US 
Ridaura Capsule 3 mg/1 Oral Prometheus Laboratories 1985-04-24 Not applicable US Ridaura Capsule 3 mg Oral Xediton Pharmaceuticals Inc 1993-12-31 Not applicable Canada 
Categories
- ATC Codes
- M01CB03 — Auranofin
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as tetracarboxylic acids and derivatives. These are carboxylic acids containing exactly four carboxyl groups.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Tetracarboxylic acids and derivatives
- Direct Parent
- Tetracarboxylic acids and derivatives
- Alternative Parents
- Oxanes / Monosaccharides / Carboxylic acid esters / Sulfenyl compounds / Oxacyclic compounds / Organic transition metal salts / Organopnictogen compounds / Organophosphorus compounds / Organic oxides / Hydrocarbon derivatives show 1 more
- Substituents
- Aliphatic heteromonocyclic compound / Carbonyl group / Carboxylic acid ester / Hydrocarbon derivative / Monosaccharide / Organic metal salt / Organic oxide / Organic oxygen compound / Organic salt / Organic transition metal salt show 9 more
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- gold coordination entity, S-glycosyl compound (CHEBI:2922)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 3H04W2810V
- CAS number
- 34031-32-8
- InChI Key
- AUJRCFUBUPVWSZ-XTZHGVARSA-M
- InChI
- 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/t10-,11-,12+,13-,14+;;/m1../s1
- IUPAC Name
- [(2R,3R,4S,5R,6S)-3,4,5-tris(acetyloxy)-6-{[(triethyl-lambda5-phosphanylidene)aurio]sulfanyl}oxan-2-yl]methyl acetate
- SMILES
- CCP(CC)(CC)=[Au]S[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O
References
- Synthesis Reference
David T. Hill, Ivan Lantos, Blaine M. Sutton, "Process and intermediate for preparing auranofin." U.S. Patent US4133952, issued January, 1972.
US4133952- General References
- Jeon KI, Byun MS, Jue DM: Gold compound auranofin inhibits IkappaB kinase (IKK) by modifying Cys-179 of IKKbeta subunit. Exp Mol Med. 2003 Apr 30;35(2):61-6. [Article]
- Kim IS, Jin JY, Lee IH, Park SJ: Auranofin induces apoptosis and when combined with retinoic acid enhances differentiation of acute promyelocytic leukaemia cells in vitro. Br J Pharmacol. 2004 Jun;142(4):749-55. Epub 2004 May 24. [Article]
- Venardos K, Harrison G, Headrick J, Perkins A: Auranofin increases apoptosis and ischaemia-reperfusion injury in the rat isolated heart. Clin Exp Pharmacol Physiol. 2004 May-Jun;31(5-6):289-94. [Article]
- Hafejee A, Winhoven S, Coulson IH: Jessner's lymphocytic infiltrate responding to oral auranofin. J Dermatolog Treat. 2004 Sep;15(5):331-2. [Article]
- Rigobello MP, Folda A, Baldoin MC, Scutari G, Bindoli A: Effect of auranofin on the mitochondrial generation of hydrogen peroxide. Role of thioredoxin reductase. Free Radic Res. 2005 Jul;39(7):687-95. [Article]
- Saccoccia F, Angelucci F, Boumis G, Carotti D, Desiato G, Miele AE, Bellelli A: Thioredoxin reductase and its inhibitors. Curr Protein Pept Sci. 2014;15(6):621-46. doi: 10.2174/1389203715666140530091910. [Article]
- Burd JG: The new doctor. J Tenn Med Assoc. 1979 Feb;72(2):128-9. [Article]
- Roder C, Thomson MJ: Auranofin: repurposing an old drug for a golden new age. Drugs R D. 2015 Mar;15(1):13-20. doi: 10.1007/s40268-015-0083-y. [Article]
- Vint IA, Foreman JC, Chain BM: The gold anti-rheumatic drug auranofin governs T cell activation by enhancing oxygen free radical production. Eur J Immunol. 1994 Sep;24(9):1961-5. doi: 10.1002/eji.1830240904. [Article]
- Harper MT: Auranofin, a thioredoxin reductase inhibitor, causes platelet death through calcium overload. Platelets. 2019;30(1):98-104. doi: 10.1080/09537104.2017.1378809. Epub 2017 Dec 1. [Article]
- Fan C, Zheng W, Fu X, Li X, Wong YS, Chen T: Enhancement of auranofin-induced lung cancer cell apoptosis by selenocystine, a natural inhibitor of TrxR1 in vitro and in vivo. Cell Death Dis. 2014 Apr 24;5:e1191. doi: 10.1038/cddis.2014.132. [Article]
- Hafstrom I, Seligmann BE, Friedman MM, Gallin JI: Auranofin affects early events in human polymorphonuclear neutrophil activation by receptor-mediated stimuli. J Immunol. 1984 Apr;132(4):2007-14. [Article]
- NIH StatPearls: Inflammatory arthritis [Link]
- External Links
- Human Metabolome Database
- HMDB0015130
- KEGG Drug
- D00237
- PubChem Compound
- 70788951
- PubChem Substance
- 46507010
- ChemSpider
- 5293650
- BindingDB
- 50153291
- 1227
- ChEBI
- 2922
- ChEMBL
- CHEMBL1366
- Therapeutic Targets Database
- DAP000757
- PharmGKB
- PA448510
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Auranofin
- MSDS
- Download (27 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Active Not Recruiting Treatment Recurrent Ovarian Carcinoma / Serous Ovarian Tumor 1 2 Active Not Recruiting Treatment Tuberculosis (TB) 1 2 Completed Supportive Care Pain 1 2 Completed Treatment Chronic Lymphocytic Leukemia (CLL) / Prolymphocytic Leukaemia (PLL) / Small Lymphocytic Lymphoma 1 2 Recruiting Treatment Dysentery, Amebic / Giardiasis 1 1 Completed Treatment Amoebiasis 1 1 Withdrawn Treatment Non-small Cell Lung Cancer (NSCLC), Recurrent / Unspecified Adult Solid Tumor, Protocol Specific 1 1, 2 Active Not Recruiting Treatment Glioblastoma Multiforme (GBM) 1 1, 2 Recruiting Treatment Adenocarcinoma of Lung (Disorder) / Advanced Non Small Cell Lung Cancer (NSCLC) / Extensive Stage Small Cell Lung Carcinoma / Recurrent Non-Small Cell Lung Carcinoma / Recurrent Small Cell Lung Carcinoma / Squamous Cell Lung Carcinoma / Stage IIIA Non Small Cell Lung Cancer / Stage IIIB Non Small Cell Lung Cancer 1 1, 2 Withdrawn Treatment Human Immunodeficiency Virus (HIV) Infections 1
Pharmacoeconomics
- Manufacturers
- Prometheus laboratories inc
- Packagers
- Catalent Pharma Solutions
- Murfreesboro Pharmaceutical Nursing Supply
- Prometheus Laboratories Inc.
- Dosage Forms
Form Route Strength Tablet, coated Capsule Oral 3 mg Capsule Oral 3 mg/1 Tablet, film coated - Prices
Unit description Cost Unit Ridaura 3 mg capsule 5.17USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 110-111 McGusty, E.R. and Sutton, B.M.; U S . Patent 3,708,579; January 2, 1973; assigned to SmithKline and French Laboratories. Nemeth, P.E. and Sutton, B.M.; U.S. Patent 3,635,945; January 18, 1972; assigned to SmithKline and French Laboratories. - Predicted Properties
Property Value Source Water Solubility 0.151 mg/mL ALOGPS logP 2.99 ALOGPS logP -1 ChemAxon logS -3.6 ALOGPS pKa (Strongest Basic) -4.3 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 5 ChemAxon Hydrogen Donor Count 0 ChemAxon Polar Surface Area 114.43 Å2 ChemAxon Rotatable Bond Count 15 ChemAxon Refractivity 114.88 m3·mol-1 ChemAxon Polarizability 50.82 Å3 ChemAxon Number of Rings 1 ChemAxon Bioavailability 0 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.9121 Blood Brain Barrier + 0.8738 Caco-2 permeable - 0.5433 P-glycoprotein substrate Non-substrate 0.5217 P-glycoprotein inhibitor I Inhibitor 0.6854 P-glycoprotein inhibitor II Non-inhibitor 0.9422 Renal organic cation transporter Non-inhibitor 0.855 CYP450 2C9 substrate Non-substrate 0.8171 CYP450 2D6 substrate Non-substrate 0.8205 CYP450 3A4 substrate Non-substrate 0.5218 CYP450 1A2 substrate Non-inhibitor 0.7046 CYP450 2C9 inhibitor Non-inhibitor 0.7631 CYP450 2D6 inhibitor Non-inhibitor 0.8886 CYP450 2C19 inhibitor Non-inhibitor 0.646 CYP450 3A4 inhibitor Non-inhibitor 0.7699 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8787 Ames test AMES toxic 0.5372 Carcinogenicity Non-carcinogens 0.6988 Biodegradation Not ready biodegradable 0.6641 Rat acute toxicity 3.1438 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9715 hERG inhibition (predictor II) Non-inhibitor 0.9108
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Rna polymerase iii regulatory region dna binding
- Specific Function
- Reduces hydrogen peroxide and alkyl hydroperoxides with reducing equivalents provided through the thioredoxin system. Involved in intracellular redox signaling.
- Gene Name
- PRDX5
- Uniprot ID
- P30044
- Uniprot Name
- Peroxiredoxin-5, mitochondrial
- Molecular Weight
- 22086.245 Da
References
- Rigobello MP, Scutari G, Boscolo R, Bindoli A: Induction of mitochondrial permeability transition by auranofin, a gold(I)-phosphine derivative. Br J Pharmacol. 2002 Aug;136(8):1162-8. [Article]
- Venardos K, Harrison G, Headrick J, Perkins A: Auranofin increases apoptosis and ischaemia-reperfusion injury in the rat isolated heart. Clin Exp Pharmacol Physiol. 2004 May-Jun;31(5-6):289-94. [Article]
- Rigobello MP, Folda A, Baldoin MC, Scutari G, Bindoli A: Effect of auranofin on the mitochondrial generation of hydrogen peroxide. Role of thioredoxin reductase. Free Radic Res. 2005 Jul;39(7):687-95. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Gundimeda U, Schiffman JE, Gottlieb SN, Roth BI, Gopalakrishna R: Negation of the cancer-preventive actions of selenium by over-expression of protein kinase Cepsilon and selenoprotein thioredoxin reductase. Carcinogenesis. 2009 Sep;30(9):1553-61. doi: 10.1093/carcin/bgp164. Epub 2009 Jul 3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Scaffold protein binding
- Specific Function
- Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or oth...
- Gene Name
- IKBKB
- Uniprot ID
- O14920
- Uniprot Name
- Inhibitor of nuclear factor kappa-B kinase subunit beta
- Molecular Weight
- 86563.245 Da
References
- Jeon KI, Byun MS, Jue DM: Gold compound auranofin inhibits IkappaB kinase (IKK) by modifying Cys-179 of IKKbeta subunit. Exp Mol Med. 2003 Apr 30;35(2):61-6. [Article]
- Youn HS, Lee JY, Saitoh SI, Miyake K, Hwang DH: Auranofin, as an anti-rheumatic gold compound, suppresses LPS-induced homodimerization of TLR4. Biochem Biophys Res Commun. 2006 Dec 1;350(4):866-71. Epub 2006 Sep 28. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- Roberts JR, Xiao J, Schliesman B, Parsons DJ, Shaw CF 3rd: Kinetics and Mechanism of the Reaction between Serum Albumin and Auranofin (and Its Isopropyl Analogue) in Vitro. Inorg Chem. 1996 Jan 17;35(2):424-433. [Article]
- Shaw CF 3rd, Isab AA, Coffer MT, Mirabelli CK: Gold(I) efflux from auranofin-treated red blood cells. Evidence for a glutathione-gold-albumin metabolite. Biochem Pharmacol. 1990 Sep 15;40(6):1227-34. [Article]
- Coffer MT, Shaw CF 3rd, Hormann AL, Mirabelli CK, Crooke ST: Thiol competition for Et3PAuS-albumin: a nonenzymatic mechanism for Et3PO formation. J Inorg Biochem. 1987 Jul;30(3):177-87. [Article]
- Christodoulou J, Sadler PJ, Tucker A: A new structural transition of serum albumin dependent on the state of Cys34. Detection by 1H-NMR spectroscopy. Eur J Biochem. 1994 Oct 1;225(1):363-8. [Article]
Drug created on June 13, 2005 13:24 / Updated on September 19, 2021 19:53