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Revision as of 09:51, 3 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank', 'ChEMBL').← Previous edit Latest revision as of 15:36, 6 November 2024 edit undoOAbot (talk | contribs)Bots441,761 editsm Open access bot: pmc updated in citation with #oabot. 
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{{short description|Chemical compound}}
{{Drugbox {{Drugbox
| Verifiedfields = changed | Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 396294438 | verifiedrevid = 458781657
| IUPAC_name = gold(+1) cation; 3,4,5-triacetyloxy-6- (acetyloxymethyl) oxane-2-thiolate; triethylphosphanium | IUPAC_name = Gold(+1) cation; 3,4,5-triacetyloxy-6- (acetyloxymethyl) oxane-2-thiolate; triethylphosphanium
| image = Auranofin-2D-skeletal.png
| image = Auranofin2DCSD.svg
| image2 = Auranofin-from-xtal-3D-balls.png | image2 = Auranofin-from-xtal-3D-balls.png

<!--Clinical data--> <!--Clinical data-->
| tradename = Ridaura | tradename = Ridaura
| Drugs.com = {{drugs.com|CDI|auranofin}} | Drugs.com = {{drugs.com|CDI|auranofin}}
| MedlinePlus = a685038 | MedlinePlus = a685038
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_AU = B3
| pregnancy_US = <!-- A / B / C / D / X --> | pregnancy_US = C
| pregnancy_category = | pregnancy_category =
| legal_AU = <!-- Unscheduled / S2 / S4 / S8 --> | legal_AU = S4
| legal_UK = <!-- GSL / P / POM / CD --> | legal_UK = POM
| legal_US = <!-- OTC / Rx-only --> | legal_US = Rx-only
| legal_status = | legal_status =
| routes_of_administration = ] | routes_of_administration = ]

<!--Pharmacokinetic data--> <!--Pharmacokinetic data-->
| bioavailability = 40%<ref name = kin>{{cite journal | vauthors = Kean WF, Hart L, Buchanan WW | title = Auranofin | journal = British Journal of Rheumatology | volume = 36 | issue = 5 | pages = 560–572 | date = May 1997 | pmid = 9189058 | doi = 10.1093/rheumatology/36.5.560 | doi-access = free }}</ref><ref name = MSR>{{cite web|title=Ridaura (auranofin) dosing, indications, interactions, adverse effects, and more|work=Medscape Reference|publisher=WebMD|access-date=13 March 2014|url=http://reference.medscape.com/drug/ridaura-auranofin-343186#showall}}</ref>
| bioavailability =
| protein_bound = | protein_bound = 60%<ref name = kin/><ref name = MSR/>
| metabolism = Plasma membrane of the cell removes the acetyl groups of the glucose moiety.
| metabolism =
| elimination_half-life = | elimination_half-life = 21-31 days<ref name = kin/><ref name = MSR/>
| excretion = | excretion = Urine (60%), faeces<ref name = kin/><ref name = MSR/>

<!--Identifiers--> <!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}} | CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 34031-32-8 | CAS_number = 34031-32-8
Line 34: Line 32:
| ATC_supplemental = | ATC_supplemental =
| PubChem = 6333901 | PubChem = 6333901
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 2922
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00995 | DrugBank = DB00995
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 21229878 | ChemSpiderID = 21242895
| UNII_Ref = {{fdacite|correct|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 3H04W2810V | UNII = 3H04W2810V
| KEGG_Ref = {{keggcite|changed|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00237 | KEGG = D00237
| ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = <!-- blanked - oldvalue: 1366 --> | ChEMBL = 1366
<!--Chemical data-->
⚫ | C=20 | H=35 | Au=1 | O=9 | P=1 | S=1 | charge = +
| C=20 | H=34
| molecular_weight = 679.493 g/mol
| Au=1 | O=9
⚫ | smiles = CC(=O)O1O(SP(CC)(CC)CC)(OC(C)=O)(OC(C)=O)C1OC(C)=O
⚫ | P=1 | S=1| charge = 0
| InChI = 1/C13H18O9S.C6H15P.Au/c1-5(14)18-9-10(19-6(2)15)12(21-8(4)17)22-13(23)11(9)20-7(3)16;1-4-7(5-2)6-3;/h9-13,23H,1-4H3;4-6H2,1-3H3;/t9-,10?,11+,12-,13-;;/m0../s1/rC19H33AuO9PS/c1-8-30(9-2,10-3)20-31-19-17(27-13(6)23)15(25-11(4)21)16(26-12(5)22)18(29-19)28-14(7)24/h15-19,30H,8-10H2,1-7H3/t15-,16?,17+,18-,19-/m0/s1
⚫ | smiles = CCP(=S1((((O1)COC(=O)C)OC(=O)C)OC(=O)C)OC(=O)C)(CC)CC
| InChIKey = JCUNAWURTWIACY-QHRKUSKDBZ
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C13H18O9S.C6H15P.Au/c1-5(14)18-9-10(19-6(2)15)12(21-8(4)17)22-13(23)11(9)20-7(3)16;1-4-7(5-2)6-3;/h9-13,23H,1-4H3;4-6H2,1-3H3;/t9-,10?,11+,12-,13-;;/m0../s1 | StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = JCUNAWURTWIACY-YHEXQHTOSA-N | StdInChIKey = AUJRCFUBUPVWSZ-XTZHGVARSA-M
}} }}
{{main|Gold salts}}
'''Auranofin''' is a ] classified by the ] as an ].


It has the brand name '''Ridaura'''. '''Auranofin''' is a ] classified by the ] as an ]. It has the brand name '''Ridaura'''.
⚫ ==Use in HIV infection==
⚫ Auranofin is under investigation as means of reducing the viral reservoir of ] that lies latent in the body's ]s despite treatment with ]. <ref>
. Keith Alcorn. AIDSmaps.com. Accessed 23 April 2011.</ref>


==Use==
Auranofin is used to treat ]. It improves arthritis symptoms including painful or tender and swollen joints and morning stiffness.<ref>{{MedlinePlusDrugInfo|medmaster|a685038}}</ref> Auranofin is a safer treatment compared to the more common injectable gold thiolates (] and ]), but ] of 66 clinical trials concluded that it is somewhat less effective.<ref>{{cite journal | vauthors = Felson DT, Anderson JJ, Meenan RF | title = The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two metaanalyses | journal = Arthritis and Rheumatism | volume = 33 | issue = 10 | pages = 1449–1461 | date = October 1990 | pmid = 1977391 | doi = 10.1002/art.1780331001 | doi-access = }}</ref>


The drug was approved for the treatment of rheumatoid arthritis in 1985. No longer a first-line treatment for rheumatoid arthritis, due to its adverse effects, "most of which are associated with long-term use for chronic disease. The most common adverse effects are gastrointestinal complaints such as loose stools, abdominal cramping and watery diarrhea, which can develop in the early months of treatment. The development of loose stools occurs in 40 % of patients, while watery diarrhea is reported in just 2–5 % of patients, and in most cases these symptoms were alleviated by reducing or splitting the dose".<ref>{{cite journal | vauthors = Roder C, Thomson MJ | title = Auranofin: repurposing an old drug for a golden new age | journal = Drugs in R&D | volume = 15 | issue = 1 | pages = 13–20 | date = March 2015 | pmid = 25698589 | pmc = 4359176 | doi = 10.1007/s40268-015-0083-y | doi-access = free }}</ref>
⚫ ==References==
<references />


==See also== ==Research==

* ]
⚫ ===HIV infection===
* ]
⚫ Auranofin is under investigation as a means of reducing the viral reservoir of ] that lies latent in the body's ]s despite treatment with ].<ref>
* ]
. Keith Alcorn. AIDSmaps.com. Accessed 23 April 2011.</ref> The drug was shown to reduce the amount of latent virus in monkey trials.<ref>{{cite journal | vauthors = Lewis MG, DaFonseca S, Chomont N, Palamara AT, Tardugno M, Mai A, Collins M, Wagner WL, Yalley-Ogunro J, Greenhouse J, Chirullo B, Norelli S, Garaci E, Savarino A | display-authors = 6 | title = Gold drug auranofin restricts the viral reservoir in the monkey AIDS model and induces containment of viral load following ART suspension | language = en-US | journal = AIDS | volume = 25 | issue = 11 | pages = 1347–1356 | date = July 2011 | pmid = 21505294 | doi = 10.1097/QAD.0b013e328347bd77 | s2cid = 19698337 | doi-access = free }}</ref> A human study testing auranofin and other investigational treatments is ongoing in Brazil.<ref>{{Cite news|url=https://clinicaltrials.gov/study/NCT02961829|title=Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure - Full Text View - ClinicalTrials.gov|access-date=2018-08-14|language=en}}</ref> Preliminary results show that auranofin contributed to a decrease in the viral reservoir.<ref>{{Cite news|url=https://programme.aids2018.org/PAGMaterial/PPT/4795_6436/AIDS2018_template%20rd%202.pptx |format=MS Power Point |access-date=2018-08-16|language=en|title=Auranofin plus nicotinamide impact HIV reservoir among ART suppressed HIV individuals}}</ref>

===Amebiasis===
Auranofin has been identified in a high-throughput drug screen as 10 times more potent than ] against '']'', the protozoan agent of human ]. Assays of ] 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 marked reductions of the number of parasites, the inflammatory reaction to the infestation, and the damage to the liver.<ref>{{cite journal | vauthors = Debnath A, Parsonage D, Andrade RM, He C, Cobo ER, Hirata K, Chen S, García-Rivera G, Orozco E, Martínez MB, Gunatilleke SS, Barrios AM, Arkin MR, Poole LB, McKerrow JH, Reed SL | display-authors = 6 | title = A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target | journal = Nature Medicine | volume = 18 | issue = 6 | pages = 956–960 | date = June 2012 | pmid = 22610278 | pmc = 3411919 | doi = 10.1038/nm.2758 }}</ref><ref>{{cite web | url = https://www.sciencedaily.com/releases/2012/05/120520133508.htm | title = Drug Found for Parasite That Is Major Cause of Death Worldwide | publisher = Science Daily}}</ref><ref>{{cite web | url = https://www.sciencedaily.com/releases/2012/05/120520133503.htm | title = Arthritis Drug Effective Against Global Parasite, Study Suggests | publisher = Science Daily}}</ref>

=== Acanthamoeba Keratitis and Primary Amoebic Meningoencephalitis ===
Auranofin may be useful in the prevention and control of '']'' infections, and in the treatment of primary amoebic meningoencephalitis, caused by pathogenic free-living amoebae ''Acanthamoeba'' spp. and '']'', respectively.<ref>{{cite journal | vauthors = Loufouma Mbouaka A, Leitsch D, Koehsler M, Walochnik J | title = Antimicrobial effect of auranofin against Acanthamoeba spp | journal = International Journal of Antimicrobial Agents | volume = 58 | issue = 5 | pages = 106425 | date = November 2021 | pmid = 34419578 | doi = 10.1016/j.ijantimicag.2021.106425 | s2cid = 237267846 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Peroutka-Bigus N, Bellaire BH | title = Antiparasitic Activity of Auranofin against Pathogenic Naegleria fowleri | journal = The Journal of Eukaryotic Microbiology | volume = 66 | issue = 4 | pages = 684–688 | date = July 2019 | pmid = 30520183 | doi = 10.1111/jeu.12706 | s2cid = 54468504 }}</ref>

===Tuberculosis===
In a cell-based screen, auranofin showed potent activity against replicating and non-replicating '']'' as well as other gram-positive bacteria. Auranofin protected mice from an otherwise lethal infection with ] (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.<ref>{{cite journal | vauthors = Harbut MB, Vilchèze C, Luo X, Hensler ME, Guo H, Yang B, Chatterjee AK, Nizet V, Jacobs WR, Schultz PG, Wang F | display-authors = 6 | title = Auranofin exerts broad-spectrum bactericidal activities by targeting thiol-redox homeostasis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 14 | pages = 4453–4458 | date = April 2015 | pmid = 25831516 | pmc = 4394260 | doi = 10.1073/pnas.1504022112 | doi-access = free | bibcode = 2015PNAS..112.4453H }}</ref>

===Ovarian cancer===
Drug-screening reveals auranofin induces apoptosis in ] cells '']''.<ref>{{cite journal | vauthors = Park SH, Lee JH, Berek JS, Hu MC | title = Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53 | journal = International Journal of Oncology | volume = 45 | issue = 4 | pages = 1691–1698 | date = October 2014 | pmid = 25096914 | pmc = 4151813 | doi = 10.3892/ijo.2014.2579 }}</ref><ref>{{cite journal | vauthors = Oommen D, Yiannakis D, Jha AN | title = BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin | journal = Mutation Research | volume = 784-785 | pages = 8–15 | year = 2016 | pmid = 26731315 | doi = 10.1016/j.mrfmmm.2015.11.002 }}</ref>

===Lung cancer including Adenocarcinoma===
When mice with Protein kinase Cι (PKCι)–dependent KP adenocarcinoma tumors that exhibited resistance to anti–PD-1 antibody therapy (α-PD-1) were treated with auranofin, the PKCι inhibitor auranofin inhibited KP tumor growth and sensitized these tumors to α-PD-1.
<ref>{{cite journal | vauthors = Yin N, Liu Y, Weems C, Shreeder B, Lou Y, Knutson KL, Murray NR, Fields AP | display-authors = 6 | title = Protein kinase Cι mediates immunosuppression in lung adenocarcinoma | journal = Science Translational Medicine | volume = 14 | issue = 671 | pages = eabq5931 | date = November 2022 | pmid = 36383684 | doi = 10.1126/scitranslmed.abq5931 | s2cid = 253554150 | pmc = 11457891 }}</ref> The Mayo clinic is running a clinical trial to research the effects of auranofin and sirolimus on squamous, ras mutated lung adenocarcinoma, and small cell lung cancer. <ref>{{cite web | url = https://www.mayo.edu/research/clinical-trials/cls-20115754 | title = PKCι & mTOR Inhibition With Auranofin+Sirolimus for Squamous Cell Lung Cancer | access-date = 2023-02-13}}</ref>

===COVID-19===
Auranofin may inhibit replication of SARS-CoV-2, the virus responsible for causing ] in cell culture. Inflammation may also be reduced.<ref>{{cite web |title=Georgia State Researchers Find Rheumatoid Arthritis Drug Is Effective Against Coronavirus |url=https://news.gsu.edu/2020/04/15/georgia-state-researchers-find-rheumatoid-arthritis-drug-is-effective-against-coronavirus/ |website=News Hub |access-date=15 April 2020 |date=15 April 2020}}</ref>

==Etymology==
The brand name ''Ridaura'' was coined from the phrase '' '''R'''emission-'''I'''nducing '''D'''rug + '''Aura'''nofin''. <ref> {{cite book|language=fr | vauthors = Lévy JJ, Garnier C |date=2007 |title=La chaîne des médicaments: Perspectives pluridisciplinaires |trans-title=The Drug Supply Chain: A Multidisciplinary Perspective |url=https://books.google.com/books?id=-fQNfIyHi4wC&dq=Auranofine&pg=PA298 |url-status= |url-access= |format= |location= |publisher=PUQ Presse de l'Université du Québec |isbn= 978-2760519510|archive-url= |archive-date= |via=Google Books |quote=}}</ref>

⚫ == References ==
{{reflist}}


== Further reading == == Further reading ==
{{refbegin}} {{refbegin}}
* {{cite journal | author = Jeon K, Byun M, Jue D | title = Gold compound auranofin inhibits IkappaB kinase (IKK) by modifying Cys-179 of IKKbeta subunit. | journal = Exp Mol Med | volume = 35 | issue = 2 | pages = 61–6 | year = 2003 | pmid = 12754408}} * {{cite journal | vauthors = Jeon KI, Byun MS, Jue DM | title = Gold compound auranofin inhibits IkappaB kinase (IKK) by modifying Cys-179 of IKKbeta subunit | journal = Experimental & Molecular Medicine | volume = 35 | issue = 2 | pages = 61–66 | date = April 2003 | pmid = 12754408 | doi = 10.1038/emm.2003.9 | doi-access = free }}
* {{cite journal | author = Kim I, Jin J, Lee I, Park S | title = Auranofin induces apoptosis and when combined with retinoic acid enhances differentiation of acute promyelocytic leukaemia cells ''in vitro''. | journal = Br J Pharmacol | volume = 142 | issue = 4 | pages = 749–55 | year = 2004 | pmid = 15159275 | doi = 10.1038/sj.bjp.0705708 | pmc = 1575039}} * {{cite journal | vauthors = Kim IS, Jin JY, Lee IH, Park SJ | title = Auranofin induces apoptosis and when combined with retinoic acid enhances differentiation of acute promyelocytic leukaemia cells in vitro | journal = British Journal of Pharmacology | volume = 142 | issue = 4 | pages = 749–755 | date = June 2004 | pmid = 15159275 | pmc = 1575039 | doi = 10.1038/sj.bjp.0705708 }}
* {{cite journal | author = Venardos K, Harrison G, Headrick J, Perkins A | title = Auranofin increases apoptosis and ischaemia-reperfusion injury in the rat isolated heart. | journal = Clin Exp Pharmacol Physiol | volume = 31 | issue = 5–6 | pages = 289–94 | year = 2004| pmid = 15191400 | doi = 10.1111/j.1440-1681.2004.03993.x}} * {{cite journal | vauthors = Venardos K, Harrison G, Headrick J, Perkins A | title = Auranofin increases apoptosis and ischaemia-reperfusion injury in the rat isolated heart | journal = Clinical and Experimental Pharmacology & Physiology | volume = 31 | issue = 5–6 | pages = 289–294 | year = 2004 | pmid = 15191400 | doi = 10.1111/j.1440-1681.2004.03993.x | s2cid = 31546992 }}
* {{cite journal | author = Hafejee A, Winhoven S, Coulson I | title = Jessner's lymphocytic infiltrate responding to oral auranofin | journal = J Dermatolog Treat | volume = 15 | issue = 5 | pages = 331–2 | year = 2004 | pmid = 15370403 | doi = 10.1080/09546630410016924}} * {{cite journal | vauthors = Hafejee A, Winhoven S, Coulson IH | title = Jessner's lymphocytic infiltrate responding to oral auranofin | journal = The Journal of Dermatological Treatment | volume = 15 | issue = 5 | pages = 331–332 | date = September 2004 | pmid = 15370403 | doi = 10.1080/09546630410016924 | s2cid = 32504211 }}
* {{cite journal | author = Rigobello M, Folda A, Baldoin M, Scutari G, Bindoli A | title = Effect of auranofin on the mitochondrial generation of hydrogen peroxide. Role of thioredoxin reductase | journal = Free Radic Res | volume = 39 | issue = 7 | pages = 687–95 | year = 2005 | pmid = 16036347 | doi = 10.1080/10715760500135391}} * {{cite journal | vauthors = Rigobello MP, Folda A, Baldoin MC, Scutari G, Bindoli A | title = Effect of auranofin on the mitochondrial generation of hydrogen peroxide. Role of thioredoxin reductase | journal = Free Radical Research | volume = 39 | issue = 7 | pages = 687–695 | date = July 2005 | pmid = 16036347 | doi = 10.1080/10715760500135391 | s2cid = 9443834 }}
* {{cite journal | author = Suarez-Almazor ME, Spooner CH, Belseck E, Shea B | title = Auranofin versus placebo in rheumatoid arthritis | journal = Cochrane Database Syst Rev | volume = | issue = 2 | pages = CD002048 | year = 2000 | pmid = 10796461 | doi = 10.1002/14651858.CD002048 | url = | issn = | editor1-last = Suarez-Almazor | editor1-first = Maria E }} * {{cite journal | vauthors = Suarez-Almazor ME, Spooner CH, Belseck E, Shea B | title = Auranofin versus placebo in rheumatoid arthritis | journal = The Cochrane Database of Systematic Reviews | volume = 2000 | issue = 2 | pages = CD002048 | year = 2000 | pmid = 10796461 | pmc = 8436883 | doi = 10.1002/14651858.CD002048 | veditors = Suarez-Almazor ME }}
{{refend}} {{refend}}


==External links== == External links ==
*{{Commons category-inline}}
* {{MedlinePlusDrugInfo|medmaster|a685038}} * {{MedlinePlusDrugInfo|medmaster|a685038}}

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{{Antirheumatic products}} {{Antirheumatic products}}
{{Gold compounds}} {{Gold compounds}}


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{{musculoskeletal-drug-stub}}
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