Auranofin is used to treat rheumatoid arthritis. It improves arthritis symptoms including painful or tender and swollen joints and morning stiffness.[4] 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.[5]
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".[6]
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.[7] The drug was shown to reduce the amount of latent virus in monkey trials.[8] A human study testing auranofin and other investigational treatments is ongoing in Brazil.[9] Preliminary results show that auranofin contributed to a decrease in the viral reservoir.[10]
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.[11][12][13]
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.[14][15]
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.[16]
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.
[19] 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. [20]
^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): 1449–1461. doi:10.1002/art.1780331001. PMID1977391.
^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. PMID30520183. S2CID54468504.
^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. PMID26731315.
^Yin N, Liu Y, Weems C, Shreeder B, Lou Y, Knutson KL, et al. (November 2022). "Protein kinase Cι mediates immunosuppression in lung adenocarcinoma". Science Translational Medicine. 14 (671): eabq5931. doi:10.1126/scitranslmed.abq5931. PMID36383684. S2CID253554150.
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): 289–294. doi:10.1111/j.1440-1681.2004.03993.x. PMID15191400. S2CID31546992.
Hafejee A, Winhoven S, Coulson IH (September 2004). "Jessner's lymphocytic infiltrate responding to oral auranofin". The Journal of Dermatological Treatment. 15 (5): 331–332. doi:10.1080/09546630410016924. PMID15370403. S2CID32504211.
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): 687–695. doi:10.1080/10715760500135391. PMID16036347. S2CID9443834.
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