Identification

Name
Auranofin
Accession Number
DB00995  (APRD00808)
Type
Small Molecule
Groups
Approved
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
  • (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
  • Auranofina
  • Auranofine
  • Auranofinum
  • Triethylphosphine gold
External IDs
SK&F 39162 / SK&F-39162
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RidauraCapsule3 mg/1OralPrometheus Laboratories1985-04-24Not applicableUs
RidauraCapsule3 mgOralXediton Pharmaceuticals Inc1993-12-31Not applicableCanada
RidauraCapsule3 mg/1OralSebela Pharmaceuticals Inc.2016-12-15Not applicableUs
Categories
UNII
3H04W2810V
CAS number
34031-32-8
Weight
Average: 678.484
Monoisotopic: 678.132666497
Chemical Formula
C20H34AuO9PS
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

Pharmacology

Indication

Used in the treatment of active, progressive or destructive forms of inflammatory arthritis, such as adult rheumatoid arthritis.

Structured Indications
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

Exactly 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.

TargetActionsOrganism
APeroxiredoxin-5, mitochondrial
inhibitor
Human
AInhibitor of nuclear factor kappa-B kinase subunit beta
inhibitor
Human
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
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).

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
  • Take with food to reduce irritation.

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. [PubMed:12754408]
  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:15159275]
  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:15191400]
  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:15370403]
  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:16036347]
External Links
Human Metabolome Database
HMDB15130
KEGG Drug
D00237
PubChem Substance
46507010
ChemSpider
5293650
BindingDB
50153291
ChEBI
2922
ChEMBL
CHEMBL1366
Therapeutic Targets Database
DAP000757
PharmGKB
PA448510
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Auranofin
ATC Codes
M01CB03 — Auranofin
AHFS Codes
  • 60:00.00
PDB Entries
Not Available
FDA label
Not Available
MSDS
Download (27 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAmoebiasis1
1RecruitingTreatmentGlioblastomas1
1WithdrawnTreatmentRecurrent Non-small Cell Lung Cancer / Unspecified Adult Solid Tumor, Protocol Specific1
1, 2RecruitingTreatmentAdenocarcinoma of the Lung / 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 / Stage IV Non-Small Cell Lung Cancer1
1, 2WithdrawnTreatmentHuman Immunodeficiency Virus (HIV)1
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemia, Prolymphocytic / Small Lymphocytic Lymphoma (SLL)1
2RecruitingTreatmentDysentery, Amebic / Giardiasis1
2RecruitingTreatmentTuberculosis1
Not AvailableActive Not RecruitingTreatmentChronic Infection / Human Immunodeficiency Virus (HIV)1
Not AvailableActive Not RecruitingTreatmentRecurrent Fallopian Tube Cancer / Recurrent Ovarian Epithelial Cancer / Recurrent Primary Peritoneal Cavity Cancer1
Not AvailableCompletedSupportive CarePain1

Pharmacoeconomics

Manufacturers
  • Prometheus laboratories inc
Packagers
Dosage forms
FormRouteStrength
CapsuleOral3 mg/1
CapsuleOral3 mg
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

Taxonomy

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
Tetracarboxylic acid or derivatives / Monosaccharide / Oxane / Carboxylic acid ester / Sulfenyl compound / Organoheterocyclic compound / Organic transition metal salt / Organic metal salt / Oxacycle / Hydrocarbon derivative
show 9 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
gold coordination entity, S-glycosyl compound (CHEBI:2922)

Targets

Kind
Protein
Organism
Human
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. [PubMed:12163349]
  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:15191400]
  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:16036347]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  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. [PubMed:19578042]
Kind
Protein
Organism
Human
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. [PubMed:12754408]
  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:17034761]

Carriers

Kind
Protein
Organism
Human
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. [PubMed:11666224]
  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:2403377]
  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:3655788]
  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:7925457]

Drug created on June 13, 2005 07:24 / Updated on October 02, 2017 04:50