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| Auranofin — an orally administered gold(I) coordination complex (gold–phosphine–thiolate “thiosugar” drug) originally approved as a disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis and widely studied for repurposing as a redox-targeted anticancer and anti-infective agent. It is a small-molecule metallodrug whose pharmacology is typically tracked via blood/plasma gold concentrations because intact auranofin is rapidly transformed and not reliably detected in blood. Standard abbreviation(s): AF (auranofin); primary target shorthand: TrxR/TxNRD (thioredoxin reductase). Primary mechanisms (ranked):
Bioavailability / PK relevance: Oral absorption is incomplete; clinical PK is commonly described as ~25% of the gold content absorbed. Gold is highly protein-bound and exhibits prolonged retention/long terminal half-life, so effective exposure depends strongly on dose and dosing duration. Because “gold levels” are the main measurable surrogate, cross-study comparisons should specify matrix (whole blood vs plasma) and timing (steady-state vs short course). In-vitro vs systemic exposure relevance: Many oncology cell studies use ~0.5–5 µM AF. Human short-course data at 6 mg/day for 7 days report plasma gold on the order of ~0.1–0.3 µg/mL (roughly sub-µM to ~1–1.5 µM range when expressed as gold equivalents), meaning lower in-vitro ranges can overlap clinically observed exposure surrogates, while higher µM regimens may exceed typical oral exposures unless higher doses/longer courses or formulation changes are used. Clinical evidence status: Approved for rheumatoid arthritis (historical DMARD use) but oncology use remains investigational. Multiple early-phase repurposing trials exist across hematologic and solid tumors; several completed studies have limited publicly posted outcomes, and there is no established standard-of-care anticancer indication. Pathways: 1.Thioredoxin Reductase (TrxR) Inhibition. - Most widely recognized for potently inhibiting TrxR. 2.Induction of Reactive Oxygen Species (ROS) and Oxidative Stress. 3.MMP depolarization, release of cytochrome c 4.Endoplasmic Reticulum (ER) Stress and Unfolded Protein Response (UPR) 5.Inhibition of Pro-survival Pathways (e.g., NF-κB Signaling) -ic50 for cancer typically 1-3uM, normal cell 5-10uM or higher. -Several studies animal testing antitumor efficacy have used doses in the region of 5–8 mg/kg via intraperitoneal injection or oral administration. -Auranofin’s anticancer activity is often linked to its inhibition of thioredoxin reductase, leading to increased oxidative stress. Mechanistic axes for Auranofin (Cancer vs Normal)
TSF legend: P: 0–30 min | R: 30 min–3 hr | G: >3 hr |
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| Glutathione (GSH) is a thiol antioxidant that scavenges reactive oxygen species (ROS), resulting in the formation of oxidized glutathione (GSSG). Decreased amounts of GSH and a decreased GSH/GSSG ratio in tissues are biomarkers of oxidative stress. Glutathione is a powerful antioxidant found in every cell of the body, composed of three amino acids: cysteine, glutamine, and glycine. It plays a crucial role in protecting cells from oxidative stress, detoxifying harmful substances, and supporting the immune system. cancer cells can have elevated levels of glutathione, which may help them survive in the oxidative environment created by the immune response and chemotherapy. This can make cancer cells more resistant to treatment. While glutathione can be obtained from certain foods (like fruits, vegetables, and meats), its absorption from supplements is debated. Some people take N-acetylcysteine (NAC) or other precursors to boost glutathione levels, but the effects on cancer prevention or treatment are still being studied. Depleting glutathione (GSH) to raise reactive oxygen species (ROS) is a strategy that has been explored in cancer research and therapy. Many cancer cells have altered redox states and may rely on GSH to survive. Increasing ROS levels can induce stress in these cells, potentially leading to cell death. Certain drugs and compounds can deplete GSH levels. For example, agents like buthionine sulfoximine (BSO) inhibit the synthesis of GSH, leading to its depletion. Cancer cells tend to exhibit higher levels of intracellular GSH, possibly as an adaptive response to a higher metabolism and thus higher steady-state levels of reactive oxygen species (ROS). "...intracellular glutathione (GSH) exhibits an astounding antioxidant activity in scavenging reactive oxygen species (ROS)..." "Cancer cells have a high level of GSH compared to normal cells." "...cancer cells are affluent with high antioxidant levels, especially with GSH, whose appearance at an elevated concentration of ∼10 mM (10 times less in normal cells) detoxifies the cancer cells." "Therefore, GSH depletion can be assumed to be the key strategy to amplify the oxidative stress in cancer cells, enhancing the destruction of cancer cells by fruitful cancer therapy." The loss of GSH is broadly known to be directly related to the apoptosis progression. |
| 5472- | AF, | Auranofin induces apoptosis and necrosis in HeLa cells via oxidative stress and glutathione depletion |
| - | in-vitro, | Cerv, | HeLa |
| 5459- | AF, | Auranofin Induces Lethality Driven by Reactive Oxygen Species in High-Grade Serous Ovarian Cancer Cells |
| - | in-vitro, | Ovarian, | NA |
| 2951- | PL, | AF, | Synergistic Dual Targeting of Thioredoxin and Glutathione Systems Irrespective of p53 in Glioblastoma Stem Cells |
| - | in-vitro, | GBM, | U87MG |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
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