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
Thumb
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.

Pharmacology
Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
Avoid life-threatening adverse drug events
Improve clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
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).

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

TargetActionsOrganism
APeroxiredoxin-5, mitochondrial
inhibitor
Humans
AInhibitor of nuclear factor kappa-B kinase subunit beta
inhibitor
Humans
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
Adverseeffects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
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.
DrugInteraction
AbacavirAuranofin may decrease the excretion rate of Abacavir which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Auranofin which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Auranofin which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Auranofin which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Auranofin which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Auranofin which could result in a higher serum level.
AclidiniumAuranofin may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastineAuranofin may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Auranofin which could result in a higher serum level.
Adefovir dipivoxilAdefovir dipivoxil may decrease the excretion rate of Auranofin which could result in a higher serum level.
Interactions
Identify potential medication risks
Easily 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

Products2
Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RidauraCapsule3 mg/1OralSebela Pharmaceuticals Inc.2016-12-15Not applicableUS flag
RidauraCapsule3 mg/1OralPrometheus Laboratories1985-04-24Not applicableUS flag
RidauraCapsule3 mgOralXediton Pharmaceuticals Inc1993-12-31Not applicableCanada flag

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
  1. 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]
  2. 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]
  3. 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]
  4. Hafejee A, Winhoven S, Coulson IH: Jessner's lymphocytic infiltrate responding to oral auranofin. J Dermatolog Treat. 2004 Sep;15(5):331-2. [Article]
  5. 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]
  6. 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]
  7. Burd JG: The new doctor. J Tenn Med Assoc. 1979 Feb;72(2):128-9. [Article]
  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. 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]
  13. NIH StatPearls: Inflammatory arthritis [Link]
Human Metabolome Database
HMDB0015130
KEGG Drug
D00237
PubChem Compound
70788951
PubChem Substance
46507010
ChemSpider
5293650
BindingDB
50153291
RxNav
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
PhaseStatusPurposeConditionsCount
2Active Not RecruitingTreatmentRecurrent Ovarian Carcinoma / Serous Ovarian Tumor1
2Active Not RecruitingTreatmentTuberculosis (TB)1
2CompletedSupportive CarePain1
2CompletedTreatmentChronic Lymphocytic Leukemia (CLL) / Prolymphocytic Leukaemia (PLL) / Small Lymphocytic Lymphoma1
2RecruitingTreatmentDysentery, Amebic / Giardiasis1
1CompletedTreatmentAmoebiasis1
1WithdrawnTreatmentNon-small Cell Lung Cancer (NSCLC), Recurrent / Unspecified Adult Solid Tumor, Protocol Specific1
1, 2Active Not RecruitingTreatmentGlioblastoma Multiforme (GBM)1
1, 2RecruitingTreatmentAdenocarcinoma 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 Cancer1
1, 2WithdrawnTreatmentHuman Immunodeficiency Virus (HIV) Infections1

Pharmacoeconomics

Manufacturers
  • Prometheus laboratories inc
Packagers
  • Catalent Pharma Solutions
  • Murfreesboro Pharmaceutical Nursing Supply
  • Prometheus Laboratories Inc.
Dosage Forms
FormRouteStrength
Tablet, coated
CapsuleOral3 mg
CapsuleOral3 mg/1
Tablet, film coated
Prices
Unit descriptionCostUnit
Ridaura 3 mg capsule5.17USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)110-111McGusty, 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
PropertyValueSource
Water Solubility0.151 mg/mLALOGPS
logP2.99ALOGPS
logP-1ChemAxon
logS-3.6ALOGPS
pKa (Strongest Basic)-4.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area114.43 Å2ChemAxon
Rotatable Bond Count15ChemAxon
Refractivity114.88 m3·mol-1ChemAxon
Polarizability50.82 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.9121
Blood Brain Barrier+0.8738
Caco-2 permeable-0.5433
P-glycoprotein substrateNon-substrate0.5217
P-glycoprotein inhibitor IInhibitor0.6854
P-glycoprotein inhibitor IINon-inhibitor0.9422
Renal organic cation transporterNon-inhibitor0.855
CYP450 2C9 substrateNon-substrate0.8171
CYP450 2D6 substrateNon-substrate0.8205
CYP450 3A4 substrateNon-substrate0.5218
CYP450 1A2 substrateNon-inhibitor0.7046
CYP450 2C9 inhibitorNon-inhibitor0.7631
CYP450 2D6 inhibitorNon-inhibitor0.8886
CYP450 2C19 inhibitorNon-inhibitor0.646
CYP450 3A4 inhibitorNon-inhibitor0.7699
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8787
Ames testAMES toxic0.5372
CarcinogenicityNon-carcinogens0.6988
BiodegradationNot ready biodegradable0.6641
Rat acute toxicity3.1438 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9715
hERG inhibition (predictor II)Non-inhibitor0.9108
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
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
  1. 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]
  2. 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]
  3. 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]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  5. 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
  1. 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]
  2. 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
  1. 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]
  2. 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]
  3. 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]
  4. 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