Auranofin: Past to Present, and repurposing.
1Department of Bioscience in Daily Life, Faculty of Bioresource Sciences, Nihon University, Fujisawa, Japan.
International Immunopharmacology
|November 3, 2021
Summary
Auranofin, a gold compound used for rheumatoid arthritis, inhibits inflammatory pathways and modulates oxidative stress responses. Further research is exploring its potential in cancer and infectious disease treatments.
Area of Science:
- Pharmacology
- Immunology
- Biochemistry
Background:
- Auranofin (AF) is a gold compound with a 40-year history in rheumatoid arthritis (RA) treatment, yet its precise mechanism of action is not fully understood.
- Current RA treatments include cytokine antibodies, impacting AF's clinical role.
- Ongoing trials investigate AF's repurposing for cancer and infectious diseases, including COVID-19.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying Auranofin's anti-inflammatory and cellular protective effects.
- To investigate the cellular transport mechanisms of Auranofin.
- To explore the potential of Auranofin and novel gold compounds in broader therapeutic applications.
Main Methods:
- Inhibition of inflammatory protein and mRNA induction by inflammatory stimulants.
- Activation and inhibition of key proteins involved in oxidative and electrophilic stress pathways.
- Analysis of cellular uptake and excretion mechanisms of Auranofin.
Main Results:
- Auranofin suppressed the induction of proinflammatory proteins (cyclooxygenase-2, inducible nitric oxide synthase) and their regulator (NF-κB).
- AF modulated oxidative stress pathways by activating peroxyredoxin-1, Kelch-like ECH-associated protein 1, and NF-E2-related factor 2, while inhibiting thioredoxin reductase.
- The mechanisms of AF transport into/out of cells and its impact on other drug pharmacokinetics remain to be fully elucidated.
Conclusions:
- Auranofin exerts anti-inflammatory effects by inhibiting key inflammatory mediators and modulates cellular redox balance.
- Understanding AF's transport mechanisms is crucial for its therapeutic applications.
- AF shows promise for repurposing in oncology and infectious diseases, with new gold compounds under development.
Keywords:
Arachidonic acid metabolismAuranofinCancerInfectionNF-κBNrf2RepurposingRheumatoid arthritisMore Related Videos
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