Auranofin

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Auranofin
Auranofin2DCSD.svg
Auranofin-from-xtal-3D-balls.png
Systematic (IUPAC) name
gold(+1) cation; 3,4,5-triacetyloxy-6- (acetyloxymethyl) oxane-2-thiolate; triethylphosphanium
Clinical data
Trade names Ridaura
AHFS/Drugs.com Consumer Drug Information
MedlinePlus a685038
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
Routes of
administration
Oral
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic data
Bioavailability 40%[1][2]
Protein binding 60%[1][2]
Metabolism Plasma membrane of the cell removes the acetyl groups of the glucose moiety.
Biological half-life 21-31 hours[1][2]
Excretion Urine (60%), faeces[1][2]
Identifiers
CAS Number 34031-32-8 YesY
ATC code M01CB03 (WHO)
PubChem CID 6333901
DrugBank DB00995 YesY
ChemSpider 21229878 YesY
UNII 3H04W2810V YesY
KEGG D00237 YesY
ChEBI CHEBI:2922 N
ChEMBL CHEMBL1366 N
Chemical data
Formula C20H35AuO9PS+
Molar mass 679.493 g/mol
 NYesY (what is this?)  (verify)

Auranofin is a gold complex classified by the World Health Organization as an antirheumatic agent. It has the brand name Ridaura.

Use[edit]

Auranofin is used to treat rheumatoid arthritis. It improves arthritis symptoms including painful or tender and swollen joints and morning stiffness.[3] Auranofin is suggested as a safer treatment compared to the more common injectable gold thiolates, but meta-analyses of 66 clinical trials shows that it is somewhat less effective.[4]

Research[edit]

HIV infection[edit]

Auranofin is under investigation as means of reducing the viral reservoir of HIV that lies latent in the body's T-cells despite treatment with antiretroviral therapy.[5]

Amebiasis[edit]

Auranofin has been identified in a high-throughput drug screen as 10 times more potent than metronidazole on Entamoeba histolytica, the protozoan agent of human amebiasis. Assays of thioredoxin reductase and transcriptional profiling suggest that the effect of auranofin on the enzyme enhances the sensitivity of the trophozoites to reactive oxygen-mediated killing in mouse and hamster models; the results are markedly reductions of the number of parasites, the inflammatory reaction to the infestation and the damage to the liver.[6][7][8]

Tuberculosis[edit]

In a cell-based screen, auranofin showed potent activity against replicating and non-replicating M. tuberculosis as well as other gram-positive bacteria. Auranofin protected mice from an otherwise lethal infection with methicillin-resistant S. aureus (MRSA). The drug acts in a similar manner in bacteria as in parasites by inhibiting thioredoxin reductase (TrxR). Studies in humans are needed to evaluate the potential of this drug to treat Gram-positive bacterial infections in humans.[9]

Ovarian Cancer[edit]

Drug-screening reveals auranofin induces apoptosis in ovarian cancer cells.[10]

References[edit]

  1. ^ a b c d Kean, WF; Hart, L; Buchanan, WW (May 1997). "Auranofin." (PDF). British Journal of Rheumatology. 36 (5): 560–72. doi:10.1093/rheumatology/36.5.560. PMID 9189058. 
  2. ^ a b c d "Ridaura (auranofin) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 13 March 2014. 
  3. ^ MedlinePlus DrugInfo medmaster-a685038
  4. ^ Felson, David T.; Anderson, Jennifer J.; Meenan, Robert F. (October 1990). "The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis results of two metaanalyses". Arthritis & Rheumatism. 33 (10): 1449–1461. doi:10.1002/art.1780331001. 
  5. ^ Gold-based drug shows promise in clearing HIV reservoir in monkey study. Keith Alcorn. AIDSmaps.com. Accessed 23 April 2011.
  6. ^ Debnath, Anjan; Parsonage, Derek; Andrade, Rosa M; He, Chen; Cobo, Eduardo R; Hirata, Ken; Chen, Steven; García-Rivera, Guillermina; Orozco, Esther; Martínez, Máximo B; Gunatilleke, Shamila S; Barrios, Amy M; Arkin, Michelle R; Poole, Leslie B; McKerrow, James H; Reed, Sharon L (2012). "A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target". Nature Medicine. 18 (6): 956–60. doi:10.1038/nm.2758. PMC 3411919free to read. PMID 22610278. 
  7. ^ Drug Found for Parasite That Is Major Cause of Death Worldwide
  8. ^ Arthritis Drug Effective Against Global Parasite, Study Suggests
  9. ^ Harbut, Michael B; Vilcheze, Catherine; Luo, Xiaozhou; Hensler, Mary E; Guo, Hui; Yang, Baiyuan; Chatterjee, Arnab K; Nizet, Victor; Jacobs Jr., William R; Schultz, Peter G; Wang, Feng (2015). "Auranofin exerts broad-spectrum bactericidal activities by targeting thio-redox homeostasis". PNAS. early edition 3-23-15 [1]: 4453–4458. doi:10.1073/pnas.1504022112. 
  10. ^ Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53.

Further reading[edit]

External links[edit]