Auranofin Cancer Research Results

AF, Auranofin: Click to Expand ⟱
Features:

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):

  1. Thioredoxin reductase (TXNRD1/TXNRD2; TrxR) inhibition by gold(I) → thioredoxin system suppression and loss of redox-buffering capacity
  2. ROS and redox stress escalation (secondary to TrxR blockade; often NAC-reversible in models) → apoptosis and other regulated death programs
  3. Mitochondrial dysfunction (Δψm collapse, bioenergetic stress) coupled to redox imbalance
  4. Proteostasis stress (ER stress/UPR; proteasome involvement in selected contexts) → non-apoptotic death phenotypes (model-dependent)
  5. Ferroptosis contribution in subsets of models (lipid peroxidation–dependent; context-dependent)
  6. Radiosensitization / chemosensitization via impaired antioxidant recovery and enhanced oxidative injury (context-dependent)
  7. Stress-response transcription (e.g., NRF2 activation as an adaptive resistance program in some settings; protective in normal cells)

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)

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 TXNRD1 TXNRD2 Thioredoxin system ↓ (primary) ↓ (primary) P→R Collapse of thioredoxin redox buffering Core, proximal target of AF; downstream effects track with redox reserve and compensatory antioxidant capacity rather than tumor lineage alone.
2 ROS redox stress ↑ (often primary downstream) ↑ (dose-dependent) P→R Oxidative injury signaling and death pathway engagement Frequently reversible with thiol antioxidants (e.g., NAC) in models, supporting causality; magnitude depends on baseline redox fragility.
3 Mitochondria bioenergetics Δψm ↓, ATP stress ↑ (context-dependent) Δψm ↓ (dose-dependent) R Energetic crisis and intrinsic death susceptibility Often coupled to redox imbalance; can amplify apoptosis/regulated necrosis depending on cellular checkpoints.
4 Proteostasis ER stress UPR ↑ (model-dependent) ↔/↑ (high exposure only) R→G Protein-folding overload and non-apoptotic death phenotypes Some reports implicate proteasome participation and paraptosis-like outcomes; not universal across tumor types.
5 NRF2 antioxidant response ↑ (adaptive; resistance role) ↑ (cytoprotective) R→G Transcriptional compensation to redox stress NRF2 induction can blunt AF efficacy in tumors yet protect normal tissues; net effect is (context-dependent).
6 Ferroptosis lipid peroxidation ↑ (model-dependent) ↔/↑ (stress-prone contexts) R→G Regulated death component in subsets Most consistent when AF-driven redox stress converges on lipid ROS handling; requires model-specific validation.
7 Radiosensitization chemosensitization ↑ sensitivity (context-dependent) ↑ toxicity risk (context-dependent) R→G Impaired antioxidant recovery increases treatment injury Mechanistically coherent with TrxR blockade; best supported where oxidative damage markers and combination indices are shown.
8 Ca²⁺ stress coupling ↑/↔ (secondary) ↑/↔ (secondary) R Amplifies ER mitochondrial death signaling Usually downstream of redox + organelle perturbation; include when Ca²⁺-dependent apoptosis/ER stress is explicitly demonstrated.
9 Glycolysis ATP production ↓ (context-dependent) ↔/↓ (high exposure only) R Metabolic stress that can reduce proliferative fitness Reported in some models; may be secondary to mitochondrial/redox disruption rather than a primary binding target.
10 HIF-1α hypoxia programs ↔ (model-dependent) ↔ G Context marker rather than core axis Evaluate case-by-case; AF’s primary leverage is redox enzyme inhibition, with HIF effects emerging indirectly in some systems.
11 Clinical Translation Constraint ↔ ↔ — Exposure, tolerability, and selectivity limit window Oral absorption is incomplete and gold is long-retained/protein-bound; many oncology studies rely on µM in-vitro dosing that may exceed typical oral exposure surrogates. Oncology trials exist but anticancer efficacy is not established as standard-of-care.

TSF legend: P: 0–30 min | R: 30 min–3 hr | G: >3 hr
Scientific Papers found: Click to Expand⟱
5462- AF,    Repurposing Auranofin for Oncology and Beyond: A Brief Overview of Clinical Trials as Mono- and Combination Therapy
- Review, Var, NA
AntiTum↑, Bacteria↓, TrxR↓, ChemoSen↑, Dose↝, ROS↑, Apoptosis↑, mTOR↓,
5472- AF,    Auranofin induces apoptosis and necrosis in HeLa cells via oxidative stress and glutathione depletion
- in-vitro, Cerv, HeLa
TrxR↓, AntiCan↑, TumCG↓, Apoptosis↑, necrosis↑, cl‑PARP↑, MMP↓, ROS↑, GSH↓, eff↓,
5471- AF,    Anti-Tumoral Treatment with Thioredoxin Reductase 1 Inhibitor Auranofin Fosters Regulatory T Cell and B16F10 Expansion in Mice
- vitro+vivo, Melanoma, B16-F10
TrxR1↓, AntiTum↑, ROS↑, NRF2↑, TumCD↑,
5470- AF,    Exploring a Therapeutic Gold Mine: The Antifungal Potential of the Gold-Based Antirheumatic Drug Auranofin
- Review, Var, NA
TrxR↓, other↝, IL6↑, IL8↑, NK cell⇅, COX2/PTGS2↓, NOS2↓, NRF2↑, Prx↑, Half-Life↑, Dose↝, ROS↑, NF-kB↓,
5469- AF,    Ligand supplementation restores the cancer therapy efficacy of the antirheumatic drug auranofin from serum inactivation
- in-vitro, CRC, HCT116
eff↑, Half-Life↑,
5468- AF,    The gold complex auranofin: new perspectives for cancer therapy
- Review, Var, NA
TrxR↓, ROS↑, eff↑, Apoptosis↑, TumCG↓, TumCP↓, Akt↓, NF-kB↓, DNAdam↑, eff↝, eff↓, PI3K↓, Akt↓, mTOR↓, Hif1a↓, VEGF↓, Casp3↑, CSCs↓, ATP↓, Glycolysis↓, eff↑, eff↑, MMP↓, AIF↑, toxicity↓,
5467- AF,    Auranofin Inhibition of Thioredoxin Reductase Sensitizes Lung Neuroendocrine Tumor Cells (NETs) and Small Cell Lung Cancer (SCLC) Cells to Sorafenib as well as Inhibiting SCLC Xenograft Growth
- in-vitro, Lung, NA
TrxR↓, eff↑, Dose↝, OS↑, eff↑,
5466- AF,    Auranofin Inhibition of Thioredoxin Reductase in a Preclinical Model of Small Cell Lung Cancer
- in-vivo, Lung, NA
TrxR↓, Dose↝, RadioS↑, ChemoSen↑, ROS↑, Diff↑, toxicity↓,
5465- AF,    The Thioredoxin Reductase Inhibitor Auranofin Suppresses Pulmonary Metastasis of Osteosarcoma, But Not Local Progression
- in-vitro, OS, NA
TrxR↓, ROS↑, TumCMig↓,
5464- AF,    Inhibition of Thioredoxin-Reductase by Auranofin as a Pro-Oxidant Anticancer Strategy for Glioblastoma: In Vitro and In Vivo Studies
- vitro+vivo, GBM, NA
TrxR↓, BioAv↓, ROS↑, eff↝, TET1?, BioAv↑,
5463- AF,    Will Auranofin Become a Golden New Treatment Against COVID-19?
- Review, Covid, NA
IL6↓, NF-kB↓, ATF2↓, TrxR↓, ROS↑, Apoptosis↑, IL6↓, Dose↑,
5461- AF,    Dual inhibition of thioredoxin reductase and proteasome is required for auranofin-induced paraptosis in breast cancer cells
- in-vitro, BC, MDA-MB-231 - in-vitro, Nor, MCF10
Paraptosis↑, ER Stress↑, TrxR↓, selectivity↑, toxicity↝, ROS↑, mt-TrxR1↓, mt-TrxR2↓,
5460- AF,    Auranofin radiosensitizes tumor cells through targeting thioredoxin reductase and resulting overproduction of reactive oxygen species
- vitro+vivo, Var, 4T1
RadioS↑, ROS↑, eff↓, mt-OCR↓, DNAdam↑, Apoptosis↑, TrxR↓, eff↑,
5459- AF,    Auranofin Induces Lethality Driven by Reactive Oxygen Species in High-Grade Serous Ovarian Cancer Cells
- in-vitro, Ovarian, NA
ROS↑, TrxR↓, MMP↓, Apoptosis↑, eff↓, Casp3↑, Casp7↑, DNAdam↑, eff↑, GSH↓, angioG↓, ChemoSen↑, cl‑PARP↑, eff↑,
5458- AF,    Auranofin reveals therapeutic anticancer potential by triggering distinct molecular cell death mechanisms and innate immunity in mutant p53 non-small cell lung cancer
- in-vitro, NSCLC, NA
TrxR↓, AntiCan↓, GPx4↓, DNAdam↑, toxicity↓, eff↝,
5457- AF,    Clinical pharmacokinetics of oral and injectable gold compounds
- Human, Nor, NA
*BioAv↝, *Dose↝, *Half-Life↑, *BioAv↝, *other↝,
5456- AF,    Phase I Clinical Trial Results of Auranofin, a Novel Antiparasitic Agent
- Trial, Nor, NA
*Dose?, *Half-Life↝, *Dose↑, *toxicity↝, *Bacteria↓, *Dose↑,
5455- AF,    Ridaura
- Study, PSA, NA
Dose↝, Half-Life↝,
1900- AF,    Potential Anticancer Activity of Auranofin
- Review, Var, NA
TrxR↓, ROS↑, Apoptosis↓, TumCP↓, eff↑,
2951- PL,  AF,    Synergistic Dual Targeting of Thioredoxin and Glutathione Systems Irrespective of p53 in Glioblastoma Stem Cells
- in-vitro, GBM, U87MG
GSH↓, eff↑, GSTP1/GSTπ↓,
1459- SFN,  AF,    Auranofin Enhances Sulforaphane-Mediated Apoptosis in Hepatocellular Carcinoma Hep3B Cells through Inactivation of the PI3K/Akt Signaling Pathway
- in-vitro, Liver, Hep3B - in-vitro, Liver, HepG2
eff↑, TumCCA↑, Apoptosis↑, MMP↓, BAX↑, cl‑PARP↑, Casp3↑, Casp8↑, Casp9↑, ROS↑, eff↓, PI3K↓, Akt↓, TrxR↓, BAX↑, Bcl-2∅,

Showing Research Papers: 1 to 21 of 21

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 21

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

GPx4↓, 1,   GSH↓, 3,   GSTP1/GSTπ↓, 1,   NRF2↑, 2,   Prx↑, 1,   ROS↑, 14,   TrxR↓, 15,   TrxR1↓, 1,   mt-TrxR1↓, 1,   mt-TrxR2↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

AIF↑, 1,   ATP↓, 1,   MMP↓, 4,   mt-OCR↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

Glycolysis↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 3,   Apoptosis↓, 1,   Apoptosis↑, 7,   ATF2↓, 1,   BAX↑, 2,   Bcl-2∅, 1,   Casp3↑, 3,   Casp7↑, 1,   Casp8↑, 1,   Casp9↑, 1,   necrosis↑, 1,   Paraptosis↑, 1,   TumCD↑, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↝, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

ER Stress↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 4,   cl‑PARP↑, 3,  

Cell Cycle & Senescence(tgid=11) ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

CSCs↓, 1,   Diff↑, 1,   mTOR↓, 2,   PI3K↓, 2,   TumCG↓, 2,  

Migration(tgid=13) ⓘ

TET1?, 1,   TumCMig↓, 1,   TumCP↓, 2,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   IL6↓, 2,   IL6↑, 1,   IL8↑, 1,   NF-kB↓, 3,   NK cell⇅, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1,   BioAv↑, 1,   ChemoSen↑, 3,   Dose↑, 1,   Dose↝, 5,   eff↓, 5,   eff↑, 12,   eff↝, 3,   Half-Life↑, 2,   Half-Life↝, 1,   RadioS↑, 2,   selectivity↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

IL6↓, 2,   IL6↑, 1,   NOS2↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↓, 1,   AntiCan↑, 1,   AntiTum↑, 2,   OS↑, 1,   toxicity↓, 3,   toxicity↝, 1,  

Infection & Microbiome(tgid=24) ⓘ

Bacteria↓, 1,  
Total Targets: 72

Pathway results for Effect on Normal Cells:


Transcription & Epigenetics(tgid=7) ⓘ

other↝, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↝, 2,   Dose?, 1,   Dose↑, 2,   Dose↝, 1,   Half-Life↑, 1,   Half-Life↝, 1,  

Functional Outcomes(tgid=23) ⓘ

toxicity↝, 1,  

Infection & Microbiome(tgid=24) ⓘ

Bacteria↓, 1,  
Total Targets: 9

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

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:273  Target#:%  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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