| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| ln Vitro |
GPX4-IN-19 (Compound Y19) (72 hours) showed effective anti-proliferative activity against six cancer cell lines (MCF-7, MDA-MB-231, PC-3, MDA-MB-468, PANC-1 and ASPC-1) (IC50: 0.021-0.094 μM) [1]. GPX4-IN-19 (12.5-50 nM, 2 weeks) effectively inhibited cell proliferation, while the addition of the inhibitor Ferrostatin-1 (Fer-1) reversed the inhibitory effect on the proliferation of MDA-MB-231 cells. GPX4-IN-19 (50 nM, 8 hours) caused typical morphological changes in the mitochondria of MDA-MB-231 cells, such as rupture of the outer mitochondrial membrane, reduction in mitochondrial volume, and reduction or disappearance of the inner mitochondrial cristae. GPX4-IN-19 (12.5–50 nM, 8 h) dose-dependently increased intracellular Fe²⁺ concentration, lipid peroxide (LPO) accumulation, malondialdehyde (MDA) content, and reactive oxygen species (ROS) levels in MDA-MB-231 cells. GPX4-IN-19 (12.5–50 nM, 8 h) induced DNA damage in MDA-MB-231 cells by increasing γH₂AX expression, and this DNA damage could be significantly attenuated by inhibitors such as Fer-1. GPX4-IN-19 (1 μM, 2 h) reduced the degradation temperature of GPX4 protein in MDA-MB-231 cells at the same temperature, indicating that GPX4-IN-19 reduced the thermal stability of GPX4 protein. GPX4-IN-19 (12.5 nM, 8 h) demonstrated significant resistance in MDA-MB-231 cell line variants (MDA-MB-231-RSL3 and MDA-MB-231-ML162) resistant to the GPX4 inhibitors RSL3 or ML162. GPX4-IN-19 (12.5-50 nM, 4-12 h) reduced GPX4 levels in MDA-MB-231 cells in a concentration-dependent manner. Based on time analysis, GPX4 expression began to increase at 4 h, with minimal change in xCT levels; however, GPX4 expression subsequently decreased at 8 h, while xCT expression significantly increased.
|
|---|---|
| ln Vivo |
GPX4-IN-19 (5 mg/kg, 10 mg/kg, intraperitoneal injection, every two days for 24 days) showed a tumor-dependent antitumor effect in the MDA-MB-231 tumor-bearing mouse model without causing significant weight loss, abnormal blood biochemical indicators or organ pathological damage, demonstrating good safety [1].
|
| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: MDA-MB-231 cells Tested Concentrations: 12.5 nM, 25 nM, 50 nM Incubation Duration: 2 weeks Experimental Results: Effectively inhibited cell proliferation, and the addition of the inhibitor Fer-1 reversed the inhibition of cell proliferation in MDA-MB-231 cells. Western Blot Analysis[1] Cell Types: MDA-MB-231 cells Tested Concentrations: 12.5 nM, 25 nM, 50 nM Incubation Duration: 8 h Experimental Results: Increased expression of DNA damage marker γH2AX. Decreased the level of GPX4 in a concentration-dependent manner. Didn't inhibit other proteins contained selenium, including Glutathione peroxidase 1 (GPX1) and Thioredoxin reductase 1 (TXNRD1). FTH1 was significantly decreased with the concentration change. Increased ACSL4 expression levels. Immunofluorescence[1] Cell Types: MDA-MB-231 cells Tested Concentrations: 12.5 nM, 25 nM, 50 nM Incubation Duration: 8 h Experimental Results: Reduced GPX4 level in a concentration-dependent manner in MDA-MB-231 cells. Western Blot Analysis[1] Cell Types: MDA-MB-231 cells Tested Concentrations: 12.5 nM, 25 nM, 50 nM Incubation Duration: 4 h, 8 h, 12 h Experimental Results: The expression of GPX4 increased at 4 h, and the xCT level of the upstream signaling pathway hardly changed at this time, but the expression level of GPX4 decreased and the expression level of xCT increased at 8h. |
| Animal Protocol |
Animal/Disease Models: MDA-MB-231 cells (1 × 107 cells in 200 μL suspension, mixed 1:1 with Matrigel and PBS) are subcutaneously injected into the left flank of female BALB/c nude mice (4 to 5weeks old)[1].
Doses: 5 mg/kg, 10 mg/kg Route of Administration: I.p., every two days for 24 days Experimental Results: Tumor growth was inhibited in a dose-dependent manner, tumor growth inhibition (TGI) of 72.53 % at 10 mg/kg. Ki67-positive tumor cells were decreased. GPX4 was significantly decreased compared with the control group. Revealed no apparent morphological abnormalities in major organs, including the heart, liver, spleen, lungs, and kidneys. Could not destroy the function of the liver, the kidneys, and the heart. |
| References |
| Molecular Formula |
C19H19CLFNO5
|
|---|---|
| Molecular Weight |
395.81
|
| CAS # |
3102894-57-2
|
| Appearance |
Off-white to light yellow solid powder
|
| 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 |
| 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 : ~50 mg/mL (~126.32 mM; with sonication)
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5265 mL | 12.6323 mL | 25.2646 mL | |
| 5 mM | 0.5053 mL | 2.5265 mL | 5.0529 mL | |
| 10 mM | 0.2526 mL | 1.2632 mL | 2.5265 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
