Auranofin , 金诺芬, 醋硫葡金

Auranofin is a chrysotherapeutic agent which inhibits histamine release from human basophils. Auranofin is gold-containing salt extensively used in the treatment of rheumatoid arthritis. Auranofin has antimicrobial properties and inhibits the growth of Clostridium difficile more effectively than vancomycin and metronidazole. According to in vitro studies carried out in 2020, auranofin inhibits the replication of coronavirus SARS-CoV-2 and reduces inflammation in human cells.

Auranofin is a gold-thiol complex with diverse biological activities. It inhibits thioredoxin reductase (IC50 = 0.2 µM), increases oxidation of mitochondrial peroxiredoxin 3 (PRDX3), and induces apoptosis in Jurkat T cells. Auranofin reduces the production of IL-6 and activation of JAK1 and JAK2, as well as inhibits nuclear translocation of NF-kB, in primary human synoviocytes. It is active against P. falciparum and S. mansoni in vitro when used at concentrations ranging from 1 to 10 µM. In vivo, auranofin (2 mg/kg per day) reduces the number of peripheral blood mononuclear cells (PBMCs) containing viral DNA and delays viral rebound in macaques infected with the mac251 strain of simian immunodeficiency virus (SIV). Auranofin (0.5 µM) synergizes with buthionine sulfoxime (BSO) to decrease glutathione peroxidase 4 (GPX4) levels, increase intracellular accumulation of reactive oxygen species (ROS), and induce ferroptosis in Huh7 and HepG2 hepatocellular carcinoma cells.

Auranofin is an orally available, lipophilic, organogold compound, used to treat rheumatoid arthritis, with anti-inflammatory and potential antineoplastic activities. Auranofin interacts with selenocysteine residue within the redox-active domain of mitochondrial thioredoxin reductase (TrxR), thereby blocking the activity of TrxR. As a result, this agent induces mitochondrial oxidative stress leading to the induction of apoptosis. Furthermore, this agent strongly inhibits the JAK1/STAT3 signal transduction pathway, thereby suppressing expression of immune factors involved in inflammation. TrxR, overexpressed in many cancer cell types, inhibits apoptosis, promotes cell growth and survival and plays a role in resistance to chemotherapy; TrxR catalyzes the reduction of oxidized thioredoxin (Trx) and plays a central role in regulating cellular redox homeostasis.

Auranofin, also known as ridaura or SK and F-39162, belongs to the class of organic compounds known as tetracarboxylic acids and derivatives. These are carboxylic acids containing exactly four carboxyl groups. Auranofin is a drug which is used in the treatment of active, progressive or destructive forms of inflammatory arthritis, such as adult rheumatoid arthritis. Auranofin exists as a solid and is considered to be practically insoluble (in water) and relatively neutral. Auranofin has been detected in multiple biofluids, such as urine and blood. Within the cell, auranofin is primarily located in the cytoplasm.

An oral chrysotherapeutic agent for the treatment of rheumatoid arthritis. Its exact mechanism of action is unknown, but it is believed to act via immunological mechanisms and alteration of lysosomal enzyme activity. Its efficacy is slightly less than that of injected gold salts, but it is better tolerated, and side effects which occur are potentially less serious.

Title: Auranofin

CAS Registry Number: 34031-32-8

CAS Name: (1-Thio-b-D-glucopyranose-2,3,4,6-tetraacetato-S)(triethylphosphine)gold

Additional Names: (2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyranosato-S)(triethylphosphine)gold; (1-thio-b-D-glucopyranosato)(triethylphosphine)gold 2,3,4,6-tetraacetate

Manufacturers' Codes: SKF-39162

Trademarks: Crisinor (Rubio); Crisofin (Allergan); Ridaura (Prometheus); Ridauran (Robapharm)

Molecular Formula: C20H34AuO9PS

Molecular Weight: 678.48

Percent Composition: C 35.40%, H 5.05%, Au 29.03%, O 21.22%, P 4.57%, S 4.73%

Literature References: Disease modifying antirheumatic drug (DMARD); orally active gold coordination complex. Prepn: E. R. McGusty, B. M. Sutton, DE 2051495; eidem, US 3635945 (1971, 1972 both to SKF). Toxicity study: B. H. Payne, D. T. Walz, Vet. Pathol. 15, Suppl. 5, 1 (1978). HPLC determn in urine: R. Kizu et al., Chem. Pharm. Bull. 41, 1261 (1993). Symposium on pharmacology and clinical experience: J. Rheumatol. 9, Suppl. 8, 1-209 (1982). Clinical trial in rheumatoid arthritis: M. Itokazu et al., Clin. Ther. 17, 60 (1995); in steroid-dependent asthma: I. L. Bernstein et al., J. Allergy Clin. Immunol. 98, 317 (1996). Review: W. F. Kean et al., Br. J. Rheumatol. 36, 560-572 (1997).

Properties: White, odorless, crystalline powder, mp 112-115°. Insol in water. Unstable to light and heat. LD50 in rats, mice (mg/kg): 265, 310 orally (Payne, Walz).

Melting point: mp 112-115°

Toxicity data: LD50 in rats, mice (mg/kg): 265, 310 orally (Payne, Walz)

Therap-Cat: Antirheumatic.

Keywords: Antiarthritic/Antirheumatic.

COA:

 (2,3,4,6-Tetra-O-acetyl-1-thio-β-D-glucopyranosato)(triethylphosphan)gold, 

CAS: 34031-32-8      M.F.: C₂₀H₃₄AuO₉PS         M.W._: 678.48