Auranofin
 | |
 | |
| Clinical data | |
|---|---|
| Trade names | Ridaura |
| AHFS/Drugs.com | Consumer Drug Information |
| MedlinePlus | a685038 |
| Pregnancy category | |
| Routes of administration | Oral |
| ATC code | M01CB03 (WHO) |
| Legal status | |
| Legal status | |
| 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  |
| PubChem (CID) | 6333901 |
| DrugBank |
DB00995 |
| ChemSpider |
21229878 |
| UNII |
3H04W2810V |
| KEGG |
D00237 |
| ChEBI |
CHEBI:2922  |
| ChEMBL |
CHEMBL1366 |
| Chemical and physical data | |
| Formula | C20H35AuO9PS+ |
| Molar mass | 679.493 g/mol |
| 3D model (Jmol) | Interactive image |
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| (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
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
HIV infection
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
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
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
Drug-screening reveals auranofin induces apoptosis in ovarian cancer cells.[10][11]
References
- 1 2 3 4 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.
- 1 2 3 4 "Ridaura (auranofin) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 13 March 2014.
- ↑ MedlinePlus DrugInfo medmaster-a685038
- ↑ 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.
- ↑ Gold-based drug shows promise in clearing HIV reservoir in monkey study. Keith Alcorn. AIDSmaps.com. Accessed 23 April 2011.
- ↑ 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 3411919
. PMID 22610278. - ↑ Drug Found for Parasite That Is Major Cause of Death Worldwide
- ↑ Arthritis Drug Effective Against Global Parasite, Study Suggests
- ↑ 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 : 4453–4458. doi:10.1073/pnas.1504022112.
- ↑ Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53.
- ↑ Oommen, Deepu, Dennis Yiannakis, and Awadhesh N. Jha. "BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin." Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 784 (2016): 8-15.
Further reading
- Jeon K, Byun M, Jue D (2003). "Gold compound auranofin inhibits IkappaB kinase (IKK) by modifying Cys-179 of IKKbeta subunit". Experimental & Molecular Medicine. 35 (2): 61–6. doi:10.1038/emm.2003.9. PMID 12754408.
- Kim I, Jin J, Lee I, Park S (2004). "Auranofin induces apoptosis and when combined with retinoic acid enhances differentiation of acute promyelocytic leukaemia cells in vitro". Br J Pharmacol. 142 (4): 749–55. doi:10.1038/sj.bjp.0705708. PMC 1575039. PMID 15159275.
- Venardos K, Harrison G, Headrick J, Perkins A (2004). "Auranofin increases apoptosis and ischaemia-reperfusion injury in the rat isolated heart". Clin Exp Pharmacol Physiol. 31 (5–6): 289–94. doi:10.1111/j.1440-1681.2004.03993.x. PMID 15191400.
- Hafejee A, Winhoven S, Coulson I (2004). "Jessner's lymphocytic infiltrate responding to oral auranofin". J Dermatolog Treat. 15 (5): 331–2. doi:10.1080/09546630410016924. PMID 15370403.
- Rigobello M, Folda A, Baldoin M, Scutari G, Bindoli A (2005). "Effect of auranofin on the mitochondrial generation of hydrogen peroxide. Role of thioredoxin reductase". Free Radic Res. 39 (7): 687–95. doi:10.1080/10715760500135391. PMID 16036347.
- Suarez-Almazor ME, Spooner CH, Belseck E, Shea B (2000). Suarez-Almazor ME, ed. "Auranofin versus placebo in rheumatoid arthritis". Cochrane Database Syst Rev (2): CD002048. doi:10.1002/14651858.CD002048. PMID 10796461.