Repositioning Candidate Details

Candidate ID: R0359
Source ID: DB00995
Source Type: approved; investigational
Compound Type: small molecule
Compound Name: Auranofin
Synonyms: (1-Thio-beta-D-glucopyranosato)(triethylphosphine)gold 2,3,4,6-tetraacetate; 2,3,4,6-Tetra-O-acetyl-1-thio-beta-D-glucopyranosato-S (triethylphosphine)gold; Auranofin; Triethylphosphine gold
Molecular Formula: C20H34AuO9PS
SMILES: CCP(CC)(CC)=[Au]S[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O
Structure:
DrugBank Description: Auranofin is a gold salt that is capable of eliciting pharmacologic actions that suppress inflammation and stimulate cell-mediated immunity. It has subsequently been listed by the World Health Organization as a member of the antirheumatic agent category. Auranofin appears to induce heme oxygenase 1 (HO-1) mRNA. Heme oxygenase 1 is an inducible heme-degrading enzyme with anti-inflammatory properties.
CAS Number: 34031-32-8
Molecular Weight: 678.484
DrugBank Indication: Used in the treatment of active, progressive or destructive forms of inflammatory arthritis, such as adult rheumatoid arthritis.
DrugBank Pharmacology: Auranofin is a gold salt used in treating inflammatory arthritis. Gold salts are called second-line drugs because they are often considered when the arthritis progresses in spite of antiinflammatory drugs (NSAIDs and corticosteroids).
DrugBank MoA: Inflammatory arthritis can cause joint swelling, warmth, pain, and tenderness; one cause of this condition is rheumatoid arthritis. In patients with rheumatoid arthritis, gold salts such as auranofin can be administered to decrease joint inflammation and prevent the destruction of bones and cartilage. Though the mechanism of action of auranofin is not fully established in rheumatoid arthritis, this drug has been shown to inhibit phagocytosis and the release of antibodies and enzymes that play a role in cytotoxic reactions, suppressing the inflammatory response. Aside from its probable immune effects in inflammatory arthritis, studies have shown that auranofin inhibits thioredoxin reductase. This enzyme has various roles in cell homeostasis, including the regulation of free radicals. Thioredoxin reductase can be over expressed in various types of tumours, rendering it an attractive target for anticancer drug development. Studies have shown that inhibiting thioredoxin reductase can cause oxidative stress and apoptosis of tumour cells by increasing the formation of free radicals. Aurofin's thiol ligand binds with high affinity to thiol and selenol groups, forming irreversible reaction products. One study showed that treatment with auranofin increased the production or reactive oxygen species and caused elevation of intracellular calcium concentration in platelets, leading to cell death. Another study showed that auranofin enhanced the production of free radicals, governing T-cell activation.
Targets: Peroxiredoxin-5, mitochondrial inhibitor; Inhibitor of nuclear factor kappa-B kinase subunit beta inhibitor
Inclusion Criteria: Therapeutic strategy associated

Strategy ID Strategy Synonyms Related Targets Related Drugs
S13 Anti-apoptosis hepatocyte apoptosis; hepatic autophagy; apoptosis Pan-caspase inhibitor Emricasan Details
S04 Anti-oxidative stress oxidative stress α-tocopherol: antioxidant Vitamin E Details
S05 Anti-inflammatory inflammatory Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name

Diseases ID DO ID Disease Name Definition Class
I15 1290 Bone disease A connective tissue disease that affects the structure or development of bone or causes an impairment of normal bone function. http://en.wikipedia.org/wiki/Bone_disease disease of anatomical entity/ musculoskeletal system disease/connective tissue disease Details