- Dual inhibition of thioredoxin reductase and proteasome is required for auranofin-induced paraptosis in breast cancer cells. [Journal Article]
- Auranofin (AF), a gold (I)-containing phosphine compound, is being investigated for oncological application as a repurposed drug. We show here that 4~5 µM AF induces paraptosis, a non-apoptotic cell death mode characterized by dilation of the endoplasmic reticulum (ER) and mitochondria, in breast cancer cells. Although the covalent inhibition of thioredoxin reductase (TrxR), an enzyme that critic…
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- Repurposing non-antifungal drugs auranofin and pentamidine in combination as fungistatic antifungal agents against C. albicans. [Journal Article]
- Fungal infection is a serious global health issue, causing approximately 1.5 million mortalities annually. However, clinically available anti-fungal drugs are limited, especially for multidrug-resistant fungal infections. Therefore, new antifungal drugs are urgently needed to address this clinical challenge. In this study, we proposed two non-antifungal drugs, auranofin and pentamidine, in combin…
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- Menadione Potentiates Auranofin-Induced Glioblastoma Cell Death. [Journal Article]
- Glioblastoma (GBM) is the most aggressive primary brain tumor. Recently, agents increasing the level of oxidative stress have been proposed as anticancer drugs. However, their efficacy may be lowered by the cytoprotective activity of antioxidant enzymes, often upregulated in neoplastic cells. Here, we assessed the mRNA and protein expression of thioredoxin reductase 1 (TrxR1), a master regulator …
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- Omics-based identification of an NRF2-related auranofin resistance signature in cancer: Insights into drug repurposing. [Journal Article]
- Auranofin is a thioredoxin reductase-1 inhibitor originally approved for the treatment of rheumatoid arthritis. Recently, auranofin has been repurposed as an anticancer drug, with pharmacological activity reported in multiple cancer types. In this study, we characterized transcriptional and genetic alterations associated with auranofin response in cancer. By integrating data from an auranofin cyt…
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- Evaluation of Auranofin Loading within Ferritin Nanocages. [Journal Article]
- Auranofin (AF), a gold(I) compound that is currently used for the treatment of rheumatoid arthritis and is in clinical trials for its promising anticancer activity, was encapsulated within the human H-chain and the horse spleen ferritin nanocages using the alkaline disassembly/reassembly protocol. The aim of the work was to highlight possible differences in their drug loading capacity and efficac…
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- Gold-Based Metal Drugs as Inhibitors of Coronavirus Proteins: The Inhibition of SARS-CoV-2 Main Protease by Auranofin and Its Analogs. [Journal Article]
- Gold compounds have a long tradition in medicine and offer many opportunities for new therapeutic applications. Herein, we evaluated the lead compound Auranofin and five related gold(I) complexes as possible inhibitors of SARS-CoV-2 Main Protease (SARS-CoV-2 Mpro), a validated drug target for the COVID-19 disease. The investigational panel of gold compounds included Auranofin; three halido analog…
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- Disruption of RBMS3 suppresses PD-L1 and enhances antitumor immune activities and therapeutic effects of auranofin against triple-negative breast cancer. [Journal Article]Chem Biol Interact. 2023 Jan 05; 369:110260.CB
- Programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) interaction exerts a vital role in tumor-associated immune evasion. While strategies disrupting PD-1/PD-L1 axis have shown clinical benefits in various cancers, the limited response rate prompts us to investigate the complex mechanisms underlying the molecular regulation of PD-L1. Here, we identify the RNA binding prote…
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- Correspondence on Letter regarding "Auranofin attenuates hepatic steatosis and fibrosis in nonalcoholic fatty liver disease via NRF2 and NF-κB signaling pathways". [Journal Article]Clin Mol Hepatol. 2023 Jan; 29(1):171-172.CM
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- Antimicrobial Activity of Auranofin, Cannabidivarin, and Tolfenamic Acid against Multidrug-Resistant Neisseria gonorrhoeae. [Journal Article]
- Alternative antimicrobial therapies are urgently required for the multidrug-resistant bacterial pathogen Neisseria gonorrhoeae, for which currently ceftriaxone is the only remaining recommended first-line therapy. Repurposing of drugs that are approved for other clinical applications offers an efficient approach for development of alternative antimicrobial therapies. Auranofin, cannabidivarin, an…
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- Targeted inhibition of TXNRD1 prevents cartilage extracellular matrix degeneration by activating Nrf2 pathway in osteoarthritis. [Journal Article]Biochem Biophys Res Commun. 2022 12 20; 635:267-276.BB
- Osteoarthritis, a prevalent orthopedic disease, can affect the elderly and causes impairment. The degradation and aberrant homeostasis of cartilage extracellular matrix figure pivotally in the progression of osteoarthritis. Thioredoxin systems plays a role in a wide range of biological processes, including cell proliferation, apoptosis, and oxidative stress. The present study aimed to investigate…
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- Letter regarding "Auranofin attenuates hepatic steatosis and fibrosis in nonalcoholic fatty liver disease via NRF2 and NF-κB signaling pathways". [Journal Article]Clin Mol Hepatol. 2023 Jan; 29(1):163-164.CM
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- Developing Bi-Gold Compound BGC2a to Target Mitochondria for the Elimination of Cancer Cells. [Journal Article]
- Reactive oxygen species (ROS) homeostasis and mitochondrial metabolism are critical for the survival of cancer cells, including cancer stem cells (CSCs), which often cause drug resistance and cancer relapse. Auranofin is a mono-gold anti-rheumatic drug, and it has been repurposed as an anticancer agent working by the induction of both ROS increase and mitochondrial dysfunction. Hypothetically, in…
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- Design, Synthesis, and Preclinical Activity in Ovarian Cancer Models of New Phosphanegold(I)-N-heterocyclic Carbene Complexes. [Journal Article]J Med Chem. 2022 11 10; 65(21):14424-14440.JM
- A new series of seven gold(I) complexes (1-7) containing 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) and phosphane ligands (L1-L7) were synthesized and evaluated for antitumor activity in ovarian cancer (OvCa) models. The synthesized complexes were characterized by IR, mass spectrometry and NMR spectroscopy, and complex 6 was characterized by XRD crystallography. The antiproliferative …
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- The rheumatoid arthritis drug auranofin lowers leptin levels and exerts antidiabetic effects in obese mice. [Journal Article]
- Low-grade, sustained inflammation in white adipose tissue (WAT) characterizes obesity and coincides with type 2 diabetes mellitus (T2DM). However, pharmacological targeting of inflammation lacks durable therapeutic effects in insulin-resistant conditions. Through a computational screen, we discovered that the FDA-approved rheumatoid arthritis drug auranofin improved insulin sensitivity and normal…
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- Unveiling the Potential of Innovative Gold(I) and Silver(I) Selenourea Complexes as Anticancer Agents Targeting TrxR and Cellular Redox Homeostasis. [Journal Article]Chemistry. 2022 Dec 15; 28(70):e202201898.C
- A series of NHC-based selenourea Ag(I) and Au(I) complexes were evaluated for their anticancer potential in vitro, on 2D and 3D human cancer cell systems. All NHC-based selenourea complexes possess an outstanding cytotoxic potency, which was comparable or even better than that of the reference metallodrug auranofin, and were also able to overcome both platinum-based and multi-drug resistances. In…
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- Anti-Cancer Effects of Auranofin in Human Lung Cancer Cells by Increasing Intracellular ROS Levels and Depleting GSH Levels. [Journal Article]
- Auranofin, as a thioredoxin reductase (TrxR) inhibitor, has promising anti-cancer activity in several cancer types. However, little is known about the inhibitory effect of auranofin on lung cancer cell growth. We, therefore, investigated the antigrowth effects of auranofin in various lung cancer cells with respect to cell death, reactive oxygen species (ROS), and glutathione (GSH) levels. Treatme…
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- Synthesis, chemical characterization, and biological evaluation of a novel auranofin derivative as an anticancer agent. [Journal Article]
- A novel gold(I) complex inspired by the known medicinal inorganic compounds auranofin and thimerosal, namely ethylthiosalicylate(triethylphosphine)gold(I) (AFETT hereafter), was synthesized and characterised and its structure was resolved through X-ray diffraction. The solution behavior of AFETT and its interactions with two biologically relevant proteins (i.e. human serum albumin and haemoglobin…
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- IDentif.AI-Omicron: Harnessing an AI-Derived and Disease-Agnostic Platform to Pinpoint Combinatorial Therapies for Clinically Actionable Anti-SARS-CoV-2 Intervention. [Journal Article]ACS Nano. 2022 09 27; 16(9):15141-15154.AN
- Nanomedicine-based and unmodified drug interventions to address COVID-19 have evolved over the course of the pandemic as more information is gleaned and virus variants continue to emerge. For example, some early therapies (e.g., antibodies) have experienced markedly decreased efficacy. Due to a growing concern of future drug resistant variants, current drug development strategies are seeking to f…
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- A case of treatment-resistant Jessner's lymphocytic infiltrate responsive to oral auranofin. [Case Reports]Australas J Dermatol. 2022 11; 63(4):e390-e392.AJ
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- Efficacy of auranofin as an inhibitor of desmoid progression. [Journal Article]
- Anticancer drugs and molecular targeted therapies are used for refractory desmoid-type fibromatosis (DF), but occasionally cause severe side effects. The purpose of this study was to identify an effective drug with fewer side effects against DF by drug repositioning, and evaluate its efficacy. FDA-approved drugs that inhibit the proliferation of DF cells harboring S45F mutations of CTNNB1 were sc…
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- Broad Spectrum Functional Activity of Structurally Related Monoanionic Au(III) Bis(Dithiolene) Complexes. [Journal Article]
- The biological properties of sixteen structurally related monoanionic gold (III) bis(dithiolene/ diselenolene) complexes were evaluated. The complexes differ in the nature of the heteroatom connected to the gold atom (AuS for dithiolene, AuSe for diselenolene), the substituent on the nitrogen atom of the thiazoline ring (Me, Et, Pr, iPr and Bu), the nature of the exocyclic atom or group of atoms …
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- Synergistic Microbicidal Effect of AUR and PEITC Against Staphylococcus aureus Skin Infection. [Journal Article]
- Given the increasing prevalence of Staphylococcus aureus antibiotic resistance, there is an urgent need to repurpose approved drugs with known pharmacology and toxicology as an alternative therapeutic strategy. We have reported that the sustained monotherapy of auranofin (AUR) inevitably resulted in reduced susceptibility or even the emergence of resistance to AUR in S. aureus. However, whether d…
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- Targeting of Nrf2 improves antitumoral responses by human NK cells, TIL and CAR T cells during oxidative stress. [Journal Article]
- CONCLUSIONS: These novel findings suggest that Nrf2 activation in human cytotoxic lymphocytes could be used to enhance the efficacy of adoptive cell therapy.
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- Auranofin attenuates hepatic steatosis and fibrosis in nonalcoholic fatty liver disease via NRF2 and NF- κB signaling pathways. [Journal Article]
- CONCLUSIONS: Auranofin inhibits lipogenesis and fibrosis formation and is a proposed candidate for NASH treatment.
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- Biotin-Targeted Au(I) Radiosensitizer for Cancer Synergistic Therapy by Intervening with Redox Homeostasis and Inducing Ferroptosis. [Journal Article]J Med Chem. 2022 06 23; 65(12):8401-8415.JM
- The search for highly selective sensitizers with a novel mechanism for tumor targeting therapy is of considerable interest. In this work, we have developed a series of new biotin-targeted Au(I) complexes. Through systematic biological evaluation and comparison, biotinylated Au(I) complex 3a containing a triphenylphosphine ligand was screened, as it realized both prominent efficient inhibition and…
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- Auranofin promotes antibacterial effect of doripenem against carbapenem-resistant Acinetobacter baumannii. [Journal Article]J Appl Microbiol. 2022 Sep; 133(3):1422-1433.JA
- CONCLUSIONS: Our results demonstrated that auranofin has an antibacterial effect with doripenem and an inhibitory effect on several factors related to carbapenem resistance.
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- Transcriptional changes of proteins of the thioredoxin and glutathione systems in Acanthamoeba spp. under oxidative stress - an RNA approach. [Journal Article]
- The thioredoxin (Trx) and the glutathione (GSH) systems represent important antioxidant systems in cells and in particular thioredoxin reductase (TrxR) has been shown to constitute a promising drug target in parasites. For the facultative protozoal pathogen Acanthamoeba, it was demonstrated that a bacterial TrxR as well as a TrxR, characteristic of higher eukaryotes, mammals and humans is express…
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- Bringing the Spotlight to Tau and TDP-43 in Frontotemporal Dementia: A Review of Promising Chemical Compounds. [Review]Curr Med Chem. 2022; 29(38):5903-5924.CM
- There is a wide variety of neurodegenerative diseases, among which frontotemporal dementia stands out. These are the second most frequent cause of dementia in the world and demand the search for an effective treatment. This disease is linked to the abnormal behavior of proteins, which group together to form insoluble aggregates. It has been shown that the tau protein and TDP-43 are the main prote…
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- [Construction and identification of a HEK293 cell line with stable TrxR1 overexpression]. [Journal Article]
- CONCLUSIONS: We successfully obtained a HEK293 cell line with stable TrxR1 overexpression, which shows resistance to auranofin and can be used for screening TrxR1 targeting drugs.
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