Auranofin is used to treat rheumatoid arthritis. It improves arthritis symptoms including painful or tender and swollen joints and morning stiffness.[3] Auranofin is a safer treatment compared to the more common injectable gold thiolates (gold sodium thiomalate and gold thioglucose), but meta-analysis of 66 clinical trials concluded that it is somewhat less effective.[4]
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".[5]
Research
HIV infection
Auranofin is under investigation as a means of reducing the viral reservoir of HIV that lies latent in the body's T-cells despite treatment with antiretroviral therapy.[6] The drug was shown to reduce the amount of latent virus in monkey trials.[7] A human study testing auranofin and other investigational treatments is ongoing in Brazil.[8] Preliminary results show that auranofin contributed to a decrease in the viral reservoir.[9]
Amebiasis
Auranofin has been identified in a high-throughput drug screen as 10 times more potent than metronidazole against 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 marked reductions of the number of parasites, the inflammatory reaction to the infestation, and the damage to the liver.[10][11][12]
Acanthamoeba Keratitis and Primary Amoebic Meningoencephalitis
Auranofin may be useful in the prevention and control of Acanthamoeba infections, and in the treatment of primary amoebic meningoencephalitis, caused by pathogenic free-living amoebae Acanthamoeba spp. and Naegleria fowleri, respectively.[13][14]
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.[15]
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. [18] 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. [19]
COVID-19
Auranofin may inhibit replication of SARS-CoV-2, the virus responsible for causing COVID-19 in cell culture. Inflammation may also be reduced.[20]
Etymology
The brand name Ridaura was coined from the phrase Remission-Inducing Drug + Auranofin. [21]
References
^ abcdKean WF, Hart L, Buchanan WW (May 1997). "Auranofin". British Journal of Rheumatology. 36 (5): 560–72. doi:10.1093/rheumatology/36.5.560. PMID 9189058.
^ abcd"Ridaura (auranofin) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 13 March 2014.
^Felson DT, Anderson JJ, Meenan RF (October 1990). "The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two metaanalyses". Arthritis and Rheumatism. 33 (10): 1449–61. doi:10.1002/art.1780331001. PMID 1977391.
^Roder C, Thomson MJ (March 2015). "Auranofin: repurposing an old drug for a golden new age". Drugs in R&D. 15 (1): 13–20. doi:10.1007/s40268-015-0083-y. PMC4359176. PMID 25698589.
^ Gold-based drug shows promise in clearing HIV reservoir in monkey study. Keith Alcorn. AIDSmaps.com. Accessed 23 April 2011.
^Lewis MG, DaFonseca S, Chomont N, Palamara AT, Tardugno M, Mai A, et al. (July 2011). "Gold drug auranofin restricts the viral reservoir in the monkey AIDS model and induces containment of viral load following ART suspension". AIDS. 25 (11): 1347–56. doi:10.1097/QAD.0b013e328347bd77. PMID 21505294. S2CID 19698337.
^"Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure - Full Text View - ClinicalTrials.gov". Retrieved 2018-08-14.
^"Auranofin plus nicotinamide impact HIV reservoir among ART suppressed HIV individuals". Retrieved 2018-08-16.
^Debnath A, Parsonage D, Andrade RM, He C, Cobo ER, Hirata K, et al. (June 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. PMC3411919. PMID 22610278.
^"Drug Found for Parasite That Is Major Cause of Death Worldwide". Science Daily.
^"Arthritis Drug Effective Against Global Parasite, Study Suggests". Science Daily.
^Loufouma Mbouaka A, Leitsch D, Koehsler M, Walochnik J (August 2021). "Antimicrobial effect of auranofin against Acanthamoeba spp". International Journal of Antimicrobial Agents. 58 (5): 106425. doi:10.1016/j.ijantimicag.2021.106425. PMID 34419578. S2CID 237267846.
^Peroutka-Bigus N, Bellaire BH (July 2019). "Antiparasitic Activity of Auranofin against Pathogenic Naegleria fowleri". The Journal of Eukaryotic Microbiology. 66 (4): 684–688. doi:10.1111/jeu.12706. PMID 30520183. S2CID 54468504.
^Harbut MB, Vilchèze C, Luo X, Hensler ME, Guo H, Yang B, et al. (April 2015). "Auranofin exerts broad-spectrum bactericidal activities by targeting thiol-redox homeostasis". Proceedings of the National Academy of Sciences of the United States of America. 112 (14): 4453–8. Bibcode:2015PNAS..112.4453H. doi:10.1073/pnas.1504022112. PMC4394260. PMID 25831516.
^Park SH, Lee JH, Berek JS, Hu MC (October 2014). "Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53". International Journal of Oncology. 45 (4): 1691–8. doi:10.3892/ijo.2014.2579. PMC4151813. PMID 25096914.
^Oommen D, Yiannakis D, Jha AN (2016). "BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin". Mutation Research. 784–785: 8–15. doi:10.1016/j.mrfmmm.2015.11.002. PMID 26731315.
^Yin, Ning; Liu, Yi; Weems, Capella; Shreeder, Barath; Lou, Yanyan; Knutson, Keith L.; Murray, Nicole R.; Fields, Alan P. (2022). "Protein kinase Cι mediates immunosuppression in lung adenocarcinoma". Science Translational Medicine. 14 (671): eabq5931. doi:10.1126/scitranslmed.abq5931. PMID 36383684. S2CID 253554150.
^"PKCι & mTOR Inhibition With Auranofin+Sirolimus for Squamous Cell Lung Cancer". Retrieved 2023-02-13.
^"Georgia State Researchers Find Rheumatoid Arthritis Drug Is Effective Against Coronavirus". News Hub. 15 April 2020. Retrieved 15 April 2020.
^ Lévy, Joseph Josy; Garnier, Catherine (2007). La chaîne des médicaments: Perspectives pluridisciplinaires [The Drug Supply Chain: A Multidisciplinary Perspective] (in French). PUQ Presse de l'Université du Québec. ISBN978-2760519510 – via Google Books.
Kim IS, Jin JY, Lee IH, Park SJ (June 2004). "Auranofin induces apoptosis and when combined with retinoic acid enhances differentiation of acute promyelocytic leukaemia cells in vitro". British Journal of Pharmacology. 142 (4): 749–55. doi:10.1038/sj.bjp.0705708. PMC1575039. PMID 15159275.
Venardos K, Harrison G, Headrick J, Perkins A (2004). "Auranofin increases apoptosis and ischaemia-reperfusion injury in the rat isolated heart". Clinical and Experimental Pharmacology & Physiology. 31 (5–6): 289–94. doi:10.1111/j.1440-1681.2004.03993.x. PMID 15191400. S2CID 31546992.
Hafejee A, Winhoven S, Coulson IH (September 2004). "Jessner's lymphocytic infiltrate responding to oral auranofin". The Journal of Dermatological Treatment. 15 (5): 331–2. doi:10.1080/09546630410016924. PMID 15370403. S2CID 32504211.
Rigobello MP, Folda A, Baldoin MC, Scutari G, Bindoli A (July 2005). "Effect of auranofin on the mitochondrial generation of hydrogen peroxide. Role of thioredoxin reductase". Free Radical Research. 39 (7): 687–95. doi:10.1080/10715760500135391. PMID 16036347. S2CID 9443834.
Suarez-Almazor ME, Spooner CH, Belseck E, Shea B (2000). Suarez-Almazor ME (ed.). "Auranofin versus placebo in rheumatoid arthritis". The Cochrane Database of Systematic Reviews. 2010 (2): CD002048. doi:10.1002/14651858.CD002048. PMC8436883. PMID 10796461.
auranofin, gold, salt, classified, world, health, organization, antirheumatic, agent, brand, name, ridaura, clinical, datatrade, namesridauraahfs, drugs, comconsumer, drug, informationmedlineplusa685038pregnancycategoryau, b3routes, ofadministrationoralatc, co. Auranofin is a gold salt classified by the World Health Organization as an antirheumatic agent It has the brand name Ridaura AuranofinClinical dataTrade namesRidauraAHFS Drugs comConsumer Drug InformationMedlinePlusa685038PregnancycategoryAU B3Routes ofadministrationOralATC codeM01CB03 WHO Legal statusLegal statusAU S4 Prescription only UK POM Prescription only US onlyPharmacokinetic dataBioavailability40 1 2 Protein binding60 1 2 MetabolismPlasma membrane of the cell removes the acetyl groups of the glucose moiety Elimination half life21 31 hours 1 2 ExcretionUrine 60 faeces 1 2 IdentifiersIUPAC name Gold 1 cation 3 4 5 triacetyloxy 6 acetyloxymethyl oxane 2 thiolate triethylphosphaniumCAS Number34031 32 8 YPubChem CID6333901DrugBankDB00995 YChemSpider21242895 YUNII3H04W2810VKEGGD00237 YChEBICHEBI 2922 NChEMBLChEMBL1366 NCompTox Dashboard EPA DTXSID4020115ECHA InfoCard100 047 077Chemical and physical dataFormulaC 20H 34Au O 9P S 0Molar mass678 48 g mol 13D model JSmol Interactive imageSMILES CCP Au S C H 1 C H C H C H C H O1 COC O C OC O C OC O C OC O C CC CCInChI 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 YKey AUJRCFUBUPVWSZ XTZHGVARSA M Y N Y what is this verify Contents 1 Use 2 Research 2 1 HIV infection 2 2 Amebiasis 2 3 Acanthamoeba Keratitis and Primary Amoebic Meningoencephalitis 2 4 Tuberculosis 2 5 Ovarian cancer 2 6 Lung cancer including Adenocarcinoma 2 7 COVID 19 3 Etymology 4 References 5 Further reading 6 External linksUse EditAuranofin is used to treat rheumatoid arthritis It improves arthritis symptoms including painful or tender and swollen joints and morning stiffness 3 Auranofin is a safer treatment compared to the more common injectable gold thiolates gold sodium thiomalate and gold thioglucose but meta analysis of 66 clinical trials concluded that it is somewhat less effective 4 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 5 Research EditHIV infection Edit Auranofin is under investigation as a means of reducing the viral reservoir of HIV that lies latent in the body s T cells despite treatment with antiretroviral therapy 6 The drug was shown to reduce the amount of latent virus in monkey trials 7 A human study testing auranofin and other investigational treatments is ongoing in Brazil 8 Preliminary results show that auranofin contributed to a decrease in the viral reservoir 9 Amebiasis Edit Auranofin has been identified in a high throughput drug screen as 10 times more potent than metronidazole against 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 marked reductions of the number of parasites the inflammatory reaction to the infestation and the damage to the liver 10 11 12 Acanthamoeba Keratitis and Primary Amoebic Meningoencephalitis Edit Auranofin may be useful in the prevention and control of Acanthamoeba infections and in the treatment of primary amoebic meningoencephalitis caused by pathogenic free living amoebae Acanthamoeba spp and Naegleria fowleri respectively 13 14 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 15 Ovarian cancer Edit Drug screening reveals auranofin induces apoptosis in ovarian cancer cells in vitro 16 17 Lung cancer including Adenocarcinoma Edit When mice with Protein kinase Ci PKCi dependent KP adenocarcinoma tumors that exhibited resistance to anti PD 1 antibody therapy a PD 1 were treated with auranofin the PKCi inhibitor auranofin inhibited KP tumor growth and sensitized these tumors to a PD 1 18 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 19 COVID 19 Edit Auranofin may inhibit replication of SARS CoV 2 the virus responsible for causing COVID 19 in cell culture Inflammation may also be reduced 20 Etymology EditThe brand name Ridaura was coined from the phrase Remission Inducing Drug Auranofin 21 References Edit a b c d Kean WF Hart L Buchanan WW May 1997 Auranofin British Journal of Rheumatology 36 5 560 72 doi 10 1093 rheumatology 36 5 560 PMID 9189058 a b c d Ridaura auranofin dosing indications interactions adverse effects and more Medscape Reference WebMD Retrieved 13 March 2014 MedlinePlus DrugInfo medmaster a685038 Felson DT Anderson JJ Meenan RF October 1990 The comparative efficacy and toxicity of second line drugs in rheumatoid arthritis Results of two metaanalyses Arthritis and Rheumatism 33 10 1449 61 doi 10 1002 art 1780331001 PMID 1977391 Roder C Thomson MJ March 2015 Auranofin repurposing an old drug for a golden new age Drugs in R amp D 15 1 13 20 doi 10 1007 s40268 015 0083 y PMC 4359176 PMID 25698589 Gold based drug shows promise in clearing HIV reservoir in monkey study Keith Alcorn AIDSmaps com Accessed 23 April 2011 Lewis MG DaFonseca S Chomont N Palamara AT Tardugno M Mai A et al July 2011 Gold drug auranofin restricts the viral reservoir in the monkey AIDS model and induces containment of viral load following ART suspension AIDS 25 11 1347 56 doi 10 1097 QAD 0b013e328347bd77 PMID 21505294 S2CID 19698337 Multi Interventional Study Exploring HIV 1 Residual Replication a Step Towards HIV 1 Eradication and Sterilizing Cure Full Text View ClinicalTrials gov Retrieved 2018 08 14 Auranofin plus nicotinamide impact HIV reservoir among ART suppressed HIV individuals Retrieved 2018 08 16 Debnath A Parsonage D Andrade RM He C Cobo ER Hirata K et al June 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 Science Daily Arthritis Drug Effective Against Global Parasite Study Suggests Science Daily Loufouma Mbouaka A Leitsch D Koehsler M Walochnik J August 2021 Antimicrobial effect of auranofin against Acanthamoeba spp International Journal of Antimicrobial Agents 58 5 106425 doi 10 1016 j ijantimicag 2021 106425 PMID 34419578 S2CID 237267846 Peroutka Bigus N Bellaire BH July 2019 Antiparasitic Activity of Auranofin against Pathogenic Naegleria fowleri The Journal of Eukaryotic Microbiology 66 4 684 688 doi 10 1111 jeu 12706 PMID 30520183 S2CID 54468504 Harbut MB Vilcheze C Luo X Hensler ME Guo H Yang B et al April 2015 Auranofin exerts broad spectrum bactericidal activities by targeting thiol redox homeostasis Proceedings of the National Academy of Sciences of the United States of America 112 14 4453 8 Bibcode 2015PNAS 112 4453H doi 10 1073 pnas 1504022112 PMC 4394260 PMID 25831516 Park SH Lee JH Berek JS Hu MC October 2014 Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53 International Journal of Oncology 45 4 1691 8 doi 10 3892 ijo 2014 2579 PMC 4151813 PMID 25096914 Oommen D Yiannakis D Jha AN 2016 BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin Mutation Research 784 785 8 15 doi 10 1016 j mrfmmm 2015 11 002 PMID 26731315 Yin Ning Liu Yi Weems Capella Shreeder Barath Lou Yanyan Knutson Keith L Murray Nicole R Fields Alan P 2022 Protein kinase Ci mediates immunosuppression in lung adenocarcinoma Science Translational Medicine 14 671 eabq5931 doi 10 1126 scitranslmed abq5931 PMID 36383684 S2CID 253554150 PKCi amp mTOR Inhibition With Auranofin Sirolimus for Squamous Cell Lung Cancer Retrieved 2023 02 13 Georgia State Researchers Find Rheumatoid Arthritis Drug Is Effective Against Coronavirus News Hub 15 April 2020 Retrieved 15 April 2020 Levy Joseph Josy Garnier Catherine 2007 La chaine des medicaments Perspectives pluridisciplinaires The Drug Supply Chain A Multidisciplinary Perspective in French PUQ Presse de l Universite du Quebec ISBN 978 2760519510 via Google Books Further reading EditJeon KI Byun MS Jue DM April 2003 Gold compound auranofin inhibits IkappaB kinase IKK by modifying Cys 179 of IKKbeta subunit Experimental amp Molecular Medicine 35 2 61 6 doi 10 1038 emm 2003 9 PMID 12754408 Kim IS Jin JY Lee IH Park SJ June 2004 Auranofin induces apoptosis and when combined with retinoic acid enhances differentiation of acute promyelocytic leukaemia cells in vitro British Journal of Pharmacology 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 Clinical and Experimental Pharmacology amp Physiology 31 5 6 289 94 doi 10 1111 j 1440 1681 2004 03993 x PMID 15191400 S2CID 31546992 Hafejee A Winhoven S Coulson IH September 2004 Jessner s lymphocytic infiltrate responding to oral auranofin The Journal of Dermatological Treatment 15 5 331 2 doi 10 1080 09546630410016924 PMID 15370403 S2CID 32504211 Rigobello MP Folda A Baldoin MC Scutari G Bindoli A July 2005 Effect of auranofin on the mitochondrial generation of hydrogen peroxide Role of thioredoxin reductase Free Radical Research 39 7 687 95 doi 10 1080 10715760500135391 PMID 16036347 S2CID 9443834 Suarez Almazor ME Spooner CH Belseck E Shea B 2000 Suarez Almazor ME ed Auranofin versus placebo in rheumatoid arthritis The Cochrane Database of Systematic Reviews 2010 2 CD002048 doi 10 1002 14651858 CD002048 PMC 8436883 PMID 10796461 External links Edit Media related to Auranofin at Wikimedia Commons MedlinePlus DrugInfo medmaster a685038 Retrieved from https en wikipedia org w index php title Auranofin amp oldid 1140858566, wikipedia, wiki, book, books, library,
