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Identification
NameAuranofin
Accession NumberDB00995  (APRD00808)
Typesmall molecule
Groupsapproved
Description

Auranofin is a organogold compound classified by the World Health Organization as an antirheumatic agent. Auranofin appears to induce heme oxygenase 1 (HO-1) mRNA. Heme oxygenase 1 is an inducible heme-degrading enzyme with anti-inflammatory properties.

Structure
Thumb
Synonyms
SynonymLanguageCode
AuroafenNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
RidauraGlaxoSmithKline
Brand mixturesNot Available
Categories
CAS number34031-32-8
WeightAverage: 678.484
Monoisotopic: 678.132666497
Chemical FormulaC20H34AuO9PS
InChI KeyAUJRCFUBUPVWSZ-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-$l^{5}-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganooxygen Compounds
ClassCarbohydrates and Carbohydrate Conjugates
SubclassMonosaccharides
Direct parentHexoses
Alternative parentsOxanes; Carboxylic Acid Esters; Ethers; Enolates; Polyamines
Substituentsoxane; carboxylic acid ester; enolate; ether; polyamine; carboxylic acid derivative
Classification descriptionThis compound belongs to the hexoses. These are monosaccharides in which the sugar unit is a hexose.
Pharmacology
IndicationUsed in the treatment of active, progressive or destructive forms of inflammatory arthritis, such as adult rheumatoid arthritis.
PharmacodynamicsAuranofin 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 actionExactly how auranofin works is not well understood. It may act as an inhibitor of kappab kinase and thioredoxin reductase which would lead to a decreased immune response and decreased free radical production, respectively. In patients with inflammatory arthritis, such as adult and juvenile rheumatoid arthritis, gold salts can decrease the inflammation of the joint lining. This effect can prevent destruction of bone and cartilage.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationApproximately 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 lifeNot Available
ClearanceNot Available
ToxicityOral, 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).
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrate Non-inhibitor 0.7631
CYP450 2D6 substrate Non-inhibitor 0.8886
CYP450 2C19 substrate Non-inhibitor 0.646
CYP450 3A4 substrate 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
Pharmacoeconomics
Manufacturers
  • Prometheus laboratories inc
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
Prices
Unit descriptionCostUnit
Ridaura 3 mg capsule5.17USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point110-111McGusty, 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 solubility1.51e-01 g/lALOGPS
logP2.99ALOGPS
logP-1ChemAxon
logS-3.6ALOGPS
pKa (strongest basic)-4.3ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count0ChemAxon
polar surface area114.43ChemAxon
rotatable bond count14ChemAxon
refractivity114.89ChemAxon
polarizability50.64ChemAxon
number of rings1ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
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 Reference
  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. Pubmed
  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. Pubmed
  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. Pubmed
  4. Hafejee A, Winhoven S, Coulson IH: Jessner’s lymphocytic infiltrate responding to oral auranofin. J Dermatolog Treat. 2004 Sep;15(5):331-2. Pubmed
  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. Pubmed
External Links
ResourceLink
KEGG DrugD00237
ChEBI2922
ChEMBLCHEMBL1366
Therapeutic Targets DatabaseDAP000757
PharmGKBPA448510
Drug Product Database1916823
Drugs.comhttp://www.drugs.com/cdi/auranofin.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/rid1379.shtml
WikipediaAuranofin
ATC CodesM01CB03
AHFS Codes
  • 60:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(27 KB)
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

Targets

1. Peroxiredoxin-5, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Peroxiredoxin-5, mitochondrial P30044 Details

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. Pubmed
  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. Pubmed
  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. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  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. Epub 2009 Jul 3. Pubmed

2. Inhibitor of nuclear factor kappa-B kinase subunit beta

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Inhibitor of nuclear factor kappa-B kinase subunit beta O14920 Details

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. Pubmed
  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. Pubmed

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Serum albumin P02768 Details

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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12