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: WARNING [1] Rx-only
Pharmacokinetic data
Bioavailability 40% [2] [3]
Protein binding 60% [2] [3]
Metabolism Plasma membrane of the cell removes the acetyl groups of the glucose moiety.
Elimination half-life 21-31 days [2] [3]
Excretion Urine (60%), faeces [2] [3]
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. [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]

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. [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]

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. [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]

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. [16]

Ovarian cancer

Drug-screening reveals auranofin induces apoptosis in ovarian cancer cells in vitro . [17] [18]

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. [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]

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. [21]

Etymology

The brand name Ridaura was coined from the phrase Remission-Inducing Drug + Auranofin. [22]

Related Research Articles

<span class="mw-page-title-main">Rheumatoid arthritis</span> Type of autoimmune arthritis

Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involved, with the same joints typically involved on both sides of the body. The disease may also affect other parts of the body, including skin, eyes, lungs, heart, nerves, and blood. This may result in a low red blood cell count, inflammation around the lungs, and inflammation around the heart. Fever and low energy may also be present. Often, symptoms come on gradually over weeks to months.

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">Immunosuppressive drug</span> Drug that inhibits activity of immune system

Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system.

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

Methotrexate, 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.

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

Chloroquine is an antiparasitic medication that treats malaria. It works by increasing the levels of haeme in the blood, a substance toxic to the malarial parasite. This kills the parasite and stops the infection from spreading. 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 the NIH does not recommend its use 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">Gold-containing drugs</span> Ionic chemical compounds of the element

Gold-containing drugs are pharmaceuticals that contain gold. Sometimes these species are referred to as "gold salts". "Chrysotherapy" and "aurotherapy" are the applications of gold compounds to medicine. Research on the medicinal effects of gold began in 1935, primarily to reduce inflammation and to slow disease progression in patients with rheumatoid arthritis. The use of gold compounds has decreased since the 1980s because of numerous side effects and monitoring requirements, limited efficacy, and very slow onset of action. Most chemical compounds of gold, including some of the drugs discussed below, are not salts, but are examples of metal thiolate complexes.

<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 humans

Programmed cell death protein 1(PD-1),. PD-1 is a protein encoded in humans by the PDCD1 gene. PD-1 is a cell surface receptor on T cells 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.

<span class="mw-page-title-main">GLRX2</span> Protein-coding gene in the species Homo sapiens

Glutaredoxin 2 (GLRX2) is an enzyme that in humans encoded by the GLRX2 gene. GLRX2, also known as GRX2, is a glutaredoxin family protein and a thiol-disulfide oxidoreductase that maintains cellular thiol homeostasis. This gene consists of four exons and three introns, spanned 10 kilobase pairs, and localized to chromosome 1q31.2–31.3.

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">Tofacitinib</span> Medication

Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, polyarticular course juvenile idiopathic arthritis, and ulcerative colitis. It is a janus kinase (JAK) inhibitor, discovered and developed by the National Institutes of Health and Pfizer.

<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

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  4. MedlinePlus DrugInfo medmaster-a685038
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  12. "Drug Found for Parasite That Is Major Cause of Death Worldwide". Science Daily.
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  16. 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.
  17. 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.
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  20. "PKCι & mTOR Inhibition With Auranofin+Sirolimus for Squamous Cell Lung Cancer" . Retrieved 2023-02-13.
  21. "Georgia State Researchers Find Rheumatoid Arthritis Drug Is Effective Against Coronavirus". News Hub. 15 April 2020. Retrieved 15 April 2020.
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Further reading