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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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| Also known as CP32. Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death. As a key protein of apoptosis, caspase-3 can also cleave GSDME and induce pyroptosis. Loss of caspase activity is an important cause of tumor progression. Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy. Caspase 3 is the main effector caspase and has a key role in apoptosis. In many types of cancer, including breast, lung, and colon cancer, caspase-3 expression is reduced or absent. On the other hand, some studies have shown that high levels of caspase-3 expression can be associated with a better prognosis in certain types of cancer, such as breast cancer. This suggests that caspase-3 may play a role in the elimination of cancer cells, and that therapies aimed at activating caspase-3 may be effective in treating certain types of cancer. Procaspase-3 is a apoptotic marker protein. Prognostic significance: • High Cas3 expression: Associated with good prognosis and increased sensitivity to chemotherapy in breast, gastric, lung, and pancreatic cancers. • Low Cas3 expression: Linked to poor prognosis and increased risk of recurrence in colorectal, hepatocellular carcinoma, ovarian, and prostate cancers. |
| 5468- | AF, | The gold complex auranofin: new perspectives for cancer therapy |
| - | Review, | Var, | NA |
| 5459- | AF, | Auranofin Induces Lethality Driven by Reactive Oxygen Species in High-Grade Serous Ovarian Cancer Cells |
| - | in-vitro, | Ovarian, | NA |
| 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 |
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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