DrugBank: Auranofin (DB00995)

targets (2) carriers (1)

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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Auroafen

Salts

Not Available

Brand names

Name	Company
Ridaura

Brand mixtures

Not Available

Categories

Antirheumatic Agents, Gold

CAS number

34031-32-8

Weight

Average: 678.484
Monoisotopic: 678.132666497

Chemical Formula

C₂₀H₃₄AuO₉PS

InChI Key

InChIKey=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

Plain Text

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

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Not Available

Classes

Not Available

Substructures

Not Available

Pharmacology

Indication

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

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.

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

Pharmacoeconomics

Manufacturers

Prometheus laboratories inc

Packagers

Dosage forms

Form	Route	Strength
Capsule	Oral

Prices

Unit description	Cost	Unit
Ridaura 3 mg capsule	5.17 USD	capsule

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

solid

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
water solubility	1.51e-01 g/l	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	ChemAxon
rotatable bond count	14	ChemAxon
refractivity	114.89	ChemAxon
polarizability	50.64	ChemAxon

References

Synthesis Reference

Not Available

General Reference

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
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
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
Hafejee A, Winhoven S, Coulson IH: Jessner’s lymphocytic infiltrate responding to oral auranofin. J Dermatolog Treat. 2004 Sep;15(5):331-2. Pubmed
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

Resource	Link
KEGG Drug	D00237
ChEBI	2922
ChEMBL	2922
Therapeutic Targets Database	DAP000757
PharmGKB	PA448510
Drug Product Database	1916823
Drugs.com	http://www.drugs.com/cdi/auranofin.html
PDRhealth	http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/rid1379.shtml
Wikipedia	http://en.wikipedia.org/wiki/Auranofin

ATC Codes

M01CB03

AHFS Codes

60:00.00

PDB Entries

Not Available

FDA label

Not Available

MSDS

show (27 KB)

Interactions

Drug Interactions

Searched, but no interactions found.

Food Interactions

Take with food to reduce irritation.

Targets
1. Peroxiredoxin-5, mitochondrial Pharmacological action: yes Actions: inhibitor Reduces hydrogen peroxide and alkyl hydroperoxides with reducing equivalents provided through the thioredoxin system. Involved in intracellular redox signaling Organism class: human UniProt ID: P30044 Gene: PRDX5 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report 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. Pubmed 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 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 Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed 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 Pharmacological action: yes Actions: inhibitor Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Also phosphorylates NCOA3 Organism class: human UniProt ID: O14920 Gene: IKBKB Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report 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. Pubmed 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

Targets

1. Peroxiredoxin-5, mitochondrial

Pharmacological action: yes
Actions: inhibitor

Reduces hydrogen peroxide and alkyl hydroperoxides with reducing equivalents provided through the thioredoxin system. Involved in intracellular redox signaling

Organism class: human
UniProt ID: P30044 Link_out

Gene: PRDX5 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Also phosphorylates NCOA3

Organism class: human
UniProt ID: O14920 Link_out

Gene: IKBKB Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
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 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 colloidal osmotic pressure of blood UniProt ID: P02768 Gene: ALB Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report 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. Pubmed 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 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 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

Carriers

1. Serum albumin

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 colloidal osmotic pressure of blood

UniProt ID: P02768 Link_out

Gene: ALB

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
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
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
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

Comments

Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19