| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
STAT3 (Signal Transducer and Activator of Transcription 3) phosphorylation; Reactive Oxygen Species (ROS) generation; Ferroptosis pathway (iron-dependent and GPX4-mediated). QD394 acts as a ROS inducer, promoting lipid peroxidation and increasing intracellular ROS accumulation. It inhibits STAT3 phosphorylation and decreases the GSH/GSSG ratio, thereby inducing iron-dependent and GPX4-mediated ferroptosis. The compound also increases H2AX phosphorylation, indicating DNA damage response activation.
|
|---|---|
| ln Vitro |
With IC50 values of 0.64, 0.34, and 0.9 μM for MIA PaCa-2, PANC-1, and BxPC-3 cell lines, respectively, QD394 (0-10 μM, 24 h) is cytotoxic. Additionally, QD394 has the ability to raise H2AX phosphorylation while decreasing STAT3 phosphorylation in cells[1]. In MIA PaCa-2 cells, QD394 (1–10 μM, 4 h) causes cell death by raising ROS levels within the cell and lowering the GSH/GSSG ratio. It also causes GPX4–mediated and iron-dependent ferroptosis[1].
QD394 exhibits cytotoxicity against pancreatic cancer cell lines with IC₅0 values of 0.64 microM (MIA PaCa-2), 0.34 microM (PANC-1), and 0.9 microM (BxPC-3) at 24 hours. In MIA PaCa-2 cells (1-10 microM, 4 hours), QD394 causes cell death by raising cellular ROS levels and decreasing the GSH/GSSG ratio. It also induces GPX4-mediated and iron-dependent ferroptosis. QD394 increases H2AX phosphorylation while decreasing STAT3 phosphorylation in cells. Treatment with the compound decreases the reduced glutathione to oxidized GSH ratio (GSH/GSSG). These effects are concentration-dependent (0.5-10 microM). |
| ln Vivo |
QD394 induces ferroptosis and suppresses the proliferation of colorectal cancer via the SP1/JNK pathway. The compound significantly induces lipid peroxidation after 24 hours treatment, similar to known ferroptosis inducers such as TBHP, RSL3, and erastin. Ferroptosis induction by QD394 is confirmed by using ferroptosis inhibitors (e.g., ferrostatin-1) and iron chelators (e.g., deferoxamine, DFO), which decrease the inhibition of colony formation caused by QD394. These findings validate that QD394 triggers ferroptosis in a variety of cancer types, highlighting its potential as a broad-spectrum anticancer agent, particularly for tumors sensitive to ferroptosis induction. The compound has been shown to induce ferroptosis in multiple cancer cell lines beyond pancreatic cancer.
|
| Enzyme Assay |
Lipid peroxidation assay: Cells are treated with QD394 (1-10 microM, 24 hours). Lipid ROS levels are measured using fluorescent probes such as C11-BODIPY581/591 (2.5 microM, 30 minutes), which shifts fluorescence from red to green upon oxidation. Cells are analyzed by flow cytometry or fluorescence microscopy. Ferroptosis is confirmed by co-treatment with ferroptosis inhibitors: ferrostatin-1 (Fer-1, 1 microM) or liproxstatin-1 (Lip-1, 1 microM). Iron-dependent ferroptosis is confirmed using the iron chelator deferoxamine (DFO, 100 microM). Colony formation assays are performed to assess long-term cytotoxic effects. These inhibitors decrease QD394-induced cell death and lipid peroxidation.
|
| Cell Assay |
Cell viability assay: Cancer cells (MIA PaCa-2, PANC-1, BxPC-3 for pancreatic cancer; additional colorectal cancer cells for validation) are seeded in 96-well plates (5,000-10,000 cells/well). After 24 hours, cells are treated with QD394 (0-10 microM) for 24-72 hours. Cell viability is measured using MTT, CCK-8, or CellTiter-Glo assays. IC₅0 values are calculated from dose-response curves. STAT3 phosphorylation is assessed by Western blotting using anti-p-STAT3 (Tyr705) and total STAT3 antibodies. H2AX phosphorylation (gammaH2AX) is detected using anti-gammaH2AX antibodies. ROS levels are measured using DCFH-DA probe (10 microM, 30 minutes) with fluorescence detection at excitation/emission 485/535 nm. GSH/GSSG ratio is determined using a commercial assay kit.
|
| Animal Protocol |
Animal studies: For pancreatic or colorectal cancer xenograft models, immunodeficient mice (e.g., nude mice) are subcutaneously injected with cancer cells (e.g., MIA PaCa-2 or HCT116 cells). When tumors reach an appropriate size (e.g., 100-150 mm3), mice are randomized and treated with QD394 (doses and route to be determined based on toxicity and efficacy studies, likely 5-50 mg/kg, oral or intraperitoneal, daily or every other day for 2-4 weeks). Tumor volume is measured every 2-3 days using calipers. At the end of treatment, tumors are excised for analysis of ferroptosis markers (lipid peroxidation, 4-HNE, GPX4, ACSL4 expression), STAT3 phosphorylation, and ROS levels. Body weight and organ toxicity are monitored throughout the study. Detailed protocols for in vivo efficacy studies are available in the literature (e.g., Hu et al., J Med Chem. 2020).
|
| ADME/Pharmacokinetics |
QD394 (MW 349.39, formula C1₉H1₉N₅O2). Solubility: soluble in DMSO. For in vivo studies, formulations should be optimized based on solubility and bioavailability. Storage: Powder at -20degC (stable for 3 years). In solution at -80degC (stable for 6 months). The compound is stable in DMSO when stored at -80degC for up to 6 months. Pharmacokinetic parameters (half-life, Cmax, AUC, bioavailability) have not been extensively reported in the literature. The compound is designed as a redox modulator and should be handled carefully to avoid degradation. Detailed physicochemical properties are available in the product data sheet.
|
| Toxicity/Toxicokinetics |
In vitro studies with QD394 show that normal cells remain unaffected at concentrations that are cytotoxic to cancer cells (IC₅0 in cancer cells 0.34-0.9 microM). This selectivity suggests a favorable therapeutic window. Standard toxicological studies including acute, subchronic, and chronic toxicity have not been extensively published. As with all research compounds, appropriate safety precautions should be followed when handling QD394. Long-term toxicity, genotoxicity, and reproductive toxicity studies have not been performed. No information is available on clinical toxicity as the compound is not approved for human use.
|
| References |
[1]. Shuai Hu, et al. A Novel Redox Modulator Induces a GPX4-Mediated Cell Death That Is Dependent on Iron and Reactive Oxygen Species. J Med Chem. 2020 Sep 10;63(17):9838-9855.
|
| Additional Infomation |
QD394 was first described in a 2020 Journal of Medicinal Chemistry publication by Shuai Hu and colleagues. The compound is available for research use only and is not approved for human therapeutic use. Studies have shown that QD394 induces iron-dependent and GPX4-mediated ferroptosis, a form of regulated cell death distinct from apoptosis. The compound represents a promising lead for the development of anticancer agents, particularly for tumors that are resistant to conventional therapies. It has been studied in various cancer types including pancreatic and colorectal cancer. The compound is stable and should be stored under appropriate conditions to maintain activity.
|
| Molecular Formula |
C19H19N5O2
|
|---|---|
| Molecular Weight |
349.386463403702
|
| Exact Mass |
349.153
|
| CAS # |
2132411-21-1
|
| PubChem CID |
130408099
|
| Appearance |
Brown to black solid powder
|
| LogP |
1.7
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
26
|
| Complexity |
577
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CN1CCN(CC1)C2=CC=C(C=C2)NC3=CC(=O)C4=NC=NC=C4C3=O
|
| InChi Key |
INZGOHBCPALCGM-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C19H19N5O2/c1-23-6-8-24(9-7-23)14-4-2-13(3-5-14)22-16-10-17(25)18-15(19(16)26)11-20-12-21-18/h2-5,10-12,22H,6-9H2,1H3
|
| Chemical Name |
6-[4-(4-methylpiperazin-1-yl)anilino]quinazoline-5,8-dione
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: ~7.3 mg/mL (~21.0 mM; with ultrasonication and warming by heating to 60°C)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.73 mg/mL (2.09 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (7.3 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.73 mg/mL (2.09 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (7.3 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8621 mL | 14.3107 mL | 28.6213 mL | |
| 5 mM | 0.5724 mL | 2.8621 mL | 5.7243 mL | |
| 10 mM | 0.2862 mL | 1.4311 mL | 2.8621 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
