Clinical data | |
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Trade names | Ridaura |
AHFS/Drugs.com | Consumer Drug Information |
MedlinePlus | a685038 |
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Routes of administration | Oral |
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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] |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.047.077 |
Chemical and physical data | |
Formula | C20H34AuO9PS0 |
Molar mass | 678.48 g·mol−1 |
3D model (JSmol) | |
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Auranofin is an orally administered gold salt classified by the World Health Organization as an antirheumatic agent. It has the brand name Ridaura. Along with sodium aurothiomalate it is one of only two gold compounds currently employed in modern medicine. [4]
Auranofin is used to treat rheumatoid arthritis. It improves arthritis symptoms including painful or tender and swollen joints and morning stiffness. [5] 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. [6]
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". [7]
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. [8] The drug was shown to reduce the amount of latent virus in monkey trials. [9] A human study testing auranofin and other investigational treatments is ongoing in Brazil. [10] Preliminary results show that auranofin contributed to a decrease in the viral reservoir. [11]
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. [12] [13] [14]
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. [15] [16]
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. [17]
Drug-screening reveals auranofin induces apoptosis in ovarian cancer cells in vitro . [18] [19]
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. [20] 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. [21]
Auranofin may inhibit replication of SARS-CoV-2, the virus responsible for causing COVID-19 in cell culture. Inflammation may also be reduced. [22]
The brand name Ridaura was coined from the phrase Remission-Inducing Drug + Auranofin. [23]
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.
Zidovudine (ZDV), also known as azidothymidine (AZT), was the first antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use in combination with other antiretrovirals. It may be used to prevent mother-to-child spread during birth or after a needlestick injury or other potential exposure. It is sold both by itself and together as lamivudine/zidovudine and abacavir/lamivudine/zidovudine. It can be used by mouth or by slow injection into a vein.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
Alvocidib is a flavonoid alkaloid CDK9 kinase inhibitor under clinical development by Tolero Pharmaceuticals for the treatment of acute myeloid leukemia. It has been studied also for the treatment of arthritis and atherosclerotic plaque formation. The target of alvocidib is the positive transcription elongation factor P-TEFb. Treatment of cells with alvocidib leads to inhibition of P-TEFb and the loss of mRNA production.
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.
CUSP9 [Coordinated Undermining of Survival Paths] is one of several cancer treatment protocols using re-purposed older drugs to interfere with cancer cell's growth signaling rather than directly killing them with cytotoxic drugs. CUSP9 is a treatment specifically targeted to glioblastoma that adds to a traditional cancer cell killing drug, temozolomide, nine older, non-cytotoxic drugs to block growth factors that enhance or drive glioblastoma growth — aprepitant blocks NK-1, auranofin inhibits thioredoxin reductase, captopril inhibits angiotensin converting enzyme, celecoxib blocks cyclooxygenase-2, disulfiram blocks aldehyde dehydrogenase, itraconazole blocks Hedgehog signaling, minocycline inhibits metalloproteinase-2 and -9, quetiapine inhibits RANKL, sertraline inhibits translation-controlled tumor protein [TCTP]. These targets have been shown to be active in promoting glioblastoma growth.
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.
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.