Auranofin

Last updated
Auranofin
Auranofin2DCSD.svg
Auranofin-from-xtal-3D-balls.png
Clinical data
Trade names Ridaura
AHFS/Drugs.com Consumer Drug Information
MedlinePlus a685038
Pregnancy
category
  • AU:B3
Routes of
administration
Oral
ATC code
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.
Elimination half-life 21-31 days [1] [2]
Excretion Urine (60%), faeces [1] [2]
Identifiers
  • Gold(+1) cation; 3,4,5-triacetyloxy-6- (acetyloxymethyl) oxane-2-thiolate; triethylphosphanium
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.047.077 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C20H34AuO9PS0
Molar mass 678.48 g·mol−1
3D model (JSmol)
  • 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)CC
  • 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 Yes check.svgY
  • Key:AUJRCFUBUPVWSZ-XTZHGVARSA-M Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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

Contents

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 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]

Ovarian cancer

Drug-screening reveals auranofin induces apoptosis in ovarian cancer cells in vitro . [16] [17]

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. [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]

Related Research Articles

<span class="mw-page-title-main">Apoptosis</span> Programmed cell death in multicellular organisms

Apoptosis is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between eight and fourteen years old, each day the approximate lost is 20 to 30 billion cells.

<span class="mw-page-title-main">Antiviral drug</span> Medication used to treat a viral infection

Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from virucides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural virucides are produced by some plants such as eucalyptus and Australian tea trees.

The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy (HAART). HAART decreases the patient's total burden of HIV, maintains function of the immune system, and prevents opportunistic infections that often lead to death. HAART also prevents the transmission of HIV between serodiscordant same-sex and opposite-sex partners so long as the HIV-positive partner maintains an undetectable viral load.

<span class="mw-page-title-main">Methotrexate</span> Chemotherapy and immunosuppressant medication

Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leukemia, lung cancer, lymphoma, gestational trophoblastic disease, and osteosarcoma. Types of autoimmune diseases it is used for include psoriasis, rheumatoid arthritis, and Crohn's disease. It can be given by mouth or by injection.

<i>Acanthamoeba</i> Genus of protozoans

Acanthamoeba is a genus of amoebae that are commonly recovered from soil, fresh water, and other habitats. The genus Acanthamoeba has two stages in its life cycle, the metabolically active trophozoite stage and a dormant, stress-resistant cyst stage. In nature, Acanthamoeba species are generally free-living bacterivores. However, they are also opportunistic pathogens able to cause serious and sometimes fatal infections in humans and other animals.

Protease inhibitors (PIs) are medications that act by interfering with enzymes that cleave proteins. Some of the most well known are antiviral drugs widely used to treat HIV/AIDS, hepatitis C and COVID-19. These protease inhibitors prevent viral replication by selectively binding to viral proteases and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.

<span class="mw-page-title-main">Folinic acid</span> Derivative of folic acid used in cancer treatment

Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer and pancreatic cancer, may be used to treat folate deficiency that results in anemia, and methanol poisoning. It is taken by mouth, injection into a muscle, or injection into a vein.

<span class="mw-page-title-main">Chloroquine</span> Medication used to treat malaria

Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medication. Chloroquine is also occasionally used for amebiasis that is occurring outside the intestines, rheumatoid arthritis, and lupus erythematosus. While it has not been formally studied in pregnancy, it appears safe. It was studied to treat COVID-19 early in the pandemic, but these studies were largely halted in the summer of 2020, and is not recommended for this purpose. It is taken by mouth.

<span class="mw-page-title-main">Nelfinavir</span> Antiretroviral drug

Nelfinavir, sold under the brand name Viracept, is an antiretroviral medication used in the treatment of HIV/AIDS. Nelfinavir belongs to the class of drugs known as protease inhibitors (PIs) and like other PIs is almost always used in combination with other antiretroviral drugs.

Virus latency is the ability of a pathogenic virus to lie dormant within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection. Latency is the phase in certain viruses' life cycles in which, after initial infection, proliferation of virus particles ceases. However, the viral genome is not eradicated. The virus can reactivate and begin producing large amounts of viral progeny without the host becoming reinfected by new outside virus, and stays within the host indefinitely.

<span class="mw-page-title-main">Leflunomide</span> Chemical compound

Leflunomide, sold under the brand name Arava among others, is an immunosuppressive disease-modifying antirheumatic drug (DMARD), used in active moderate-to-severe rheumatoid arthritis and psoriatic arthritis. It is a pyrimidine synthesis inhibitor that works by inhibiting dihydroorotate dehydrogenase.

<span class="mw-page-title-main">Topotecan</span> Chemical compound

Topotecan, sold under the brand name Hycamtin among others, is a chemotherapeutic agent medication that is a topoisomerase inhibitor. It is a synthetic, water-soluble analog of the natural chemical compound camptothecin. It is used in the form of its hydrochloride salt to treat ovarian cancer, lung cancer and other cancer types.

<span class="mw-page-title-main">Miltefosine</span> Phospholipid drug

Miltefosine, sold under the trade name Impavido among others, is a medication mainly used to treat leishmaniasis and free-living amoeba infections such as Naegleria fowleri and Balamuthia mandrillaris. This includes the three forms of leishmaniasis: cutaneous, visceral and mucosal. It may be used with liposomal amphotericin B or paromomycin. It is taken by mouth.

<span class="mw-page-title-main">Sodium aurothiomalate</span> Pharmaceutical drug

Sodium aurothiomalate is a gold compound that is used for its immunosuppressive anti-rheumatic effects. Along with an orally-administered gold salt, auranofin, it is one of only two gold compounds currently employed in modern medicine.

CD4 immunoadhesin is a recombinant fusion protein consisting of a combination of CD4 and the fragment crystallizable region, similarly known as immunoglobulin. It belongs to the antibody (Ig) gene family. CD4 is a surface receptor for human immunodeficiency virus (HIV). The CD4 immunoadhesin molecular fusion allow the protein to possess key functions from each independent subunit. The CD4 specific properties include the gp120-binding and HIV-blocking capabilities. Properties specific to immunoglobulin are the long plasma half-life and Fc receptor binding. The properties of the protein means that it has potential to be used in AIDS therapy as of 2017. Specifically, CD4 immunoadhesin plays a role in antibody-dependent cell-mediated cytotoxicity (ADCC) towards HIV-infected cells. While natural anti-gp120 antibodies exhibit a response towards uninfected CD4-expressing cells that have a soluble gp120 bound to the CD4 on the cell surface, CD4 immunoadhesin, however, will not exhibit a response. One of the most relevant of these possibilities is its ability to cross the placenta.

<span class="mw-page-title-main">Antifolate</span> Class of antimetabolite medications

Antifolates are a class of antimetabolite medications that antagonise (that is, block) the actions of folic acid (vitamin B9). Folic acid's primary function in the body is as a cofactor to various methyltransferases involved in serine, methionine, thymidine and purine biosynthesis. Consequently, antifolates inhibit cell division, DNA/RNA synthesis and repair and protein synthesis. Some such as proguanil, pyrimethamine and trimethoprim selectively inhibit folate's actions in microbial organisms such as bacteria, protozoa and fungi. The majority of antifolates work by inhibiting dihydrofolate reductase (DHFR).

<span class="mw-page-title-main">Programmed cell death protein 1</span> Mammalian protein found in Homo sapiens

Programmed cell death protein 1, also known as PD-1 and CD279, is a protein on the surface of T and B cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity. This prevents autoimmune diseases, but it can also prevent the immune system from killing cancer cells.

A Janus kinase inhibitor, also known as JAK inhibitor or jakinib, is a type of immune modulating medication, which inhibits the activity of one or more of the Janus kinase family of enzymes, thereby interfering with the JAK-STAT signaling pathway in lymphocytes.

<span class="mw-page-title-main">Gold nanoparticles in chemotherapy</span> Drug delivery technique using gold nanoparticles as vectors

Gold nanoparticles in chemotherapy and radiotherapy is the use of colloidal gold in therapeutic treatments, often for cancer or arthritis. Gold nanoparticle technology shows promise in the advancement of cancer treatments. Some of the properties that gold nanoparticles possess, such as small size, non-toxicity and non-immunogenicity make these molecules useful candidates for targeted drug delivery systems. With tumor-targeting delivery vectors becoming smaller, the ability to by-pass the natural barriers and obstacles of the body becomes more probable. To increase specificity and likelihood of drug delivery, tumor specific ligands may be grafted onto the particles along with the chemotherapeutic drug molecules, to allow these molecules to circulate throughout the tumor without being redistributed into the body.

<span class="mw-page-title-main">Antiarthritics</span> Drug class

An antiarthritic is any drug used to relieve or prevent arthritic symptoms, such as joint pain or joint stiffness. Depending on the antiarthritic drug class, it is used for managing pain, reducing inflammation or acting as an immunosuppressant. These drugs are typically given orally, topically or through administration by injection. The choice of antiarthritic medication is often determined by the nature of arthritis, the severity of symptoms as well as other factors, such as the tolerability of side effects.

References

  1. 1 2 3 4 Kean WF, Hart L, Buchanan WW (May 1997). "Auranofin". British Journal of Rheumatology. 36 (5): 560–572. doi: 10.1093/rheumatology/36.5.560 . PMID   9189058.
  2. 1 2 3 4 "Ridaura (auranofin) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 13 March 2014.
  3. MedlinePlus DrugInfo medmaster-a685038
  4. 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. PMID   1977391.
  5. 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 . PMC   4359176 . PMID   25698589.
  6. Gold-based drug shows promise in clearing HIV reservoir in monkey study. Keith Alcorn. AIDSmaps.com. Accessed 23 April 2011.
  7. 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): 1347–1356. doi: 10.1097/QAD.0b013e328347bd77 . PMID   21505294. S2CID   19698337.
  8. "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.
  9. "Auranofin plus nicotinamide impact HIV reservoir among ART suppressed HIV individuals" . Retrieved 2018-08-16.
  10. 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): 956–960. doi:10.1038/nm.2758. PMC   3411919 . PMID   22610278.
  11. "Drug Found for Parasite That Is Major Cause of Death Worldwide". Science Daily.
  12. "Arthritis Drug Effective Against Global Parasite, Study Suggests". Science Daily.
  13. Loufouma Mbouaka A, Leitsch D, Koehsler M, Walochnik J (November 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.
  14. 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.
  15. 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): 4453–4458. Bibcode:2015PNAS..112.4453H. doi: 10.1073/pnas.1504022112 . PMC   4394260 . PMID   25831516.
  16. 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): 1691–1698. doi:10.3892/ijo.2014.2579. PMC   4151813 . PMID   25096914.
  17. 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.
  18. 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. PMID   36383684. S2CID   253554150.
  19. "PKCι & mTOR Inhibition With Auranofin+Sirolimus for Squamous Cell Lung Cancer" . Retrieved 2023-02-13.
  20. "Georgia State Researchers Find Rheumatoid Arthritis Drug Is Effective Against Coronavirus". News Hub. 15 April 2020. Retrieved 15 April 2020.
  21. Lévy JJ, Garnier C (2007). La chaîne des médicaments: Perspectives pluridisciplinaires [The Drug Supply Chain: A Multidisciplinary Perspective] (in French). PUQ Presse de l'Université du Québec. ISBN   978-2760519510 via Google Books.

Further reading