PROTAC GPX4 degrader-1
Based on 1 Customer Validation
PROTAC GPX4 degrader-1 is a glutathione peroxidase 4 (GPX4) PROTAC degrader with a DC50 of 30 nM. PROTAC GPX4 degrader-1 induces ROS accumulation and ferroptosis in cancer cells. PROTAC GPX4 degrader-1 inhibits cell growth and reduces GPX4 levels in tumor tissues. PROTAC GPX4 degrader-1 can be used in research related to various cancers including fibrosarcoma, non-small cell lung cancer, and melanoma.
(Pink: GPX4 ligand (HY-401204); Blue: Cereblon ligand (HY-14658); Black: linker (HY-175936)).
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Pureté : 98.53%
- CAS No.: 2916433-81-1
- Formule: C50H57ClN10O10
- Masse moléculaire:993.50
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Stockage:
4°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
Description
IC50 & Target
[1]|
GPX4 30 nM (DC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A-375 | IC50 |
0.2 μM
Compound: DC-2
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Antiproliferative activity against human A-375 cells assessed as reduction in cell viability incubated for 24 hrs by MTT assay
Antiproliferative activity against human A-375 cells assessed as reduction in cell viability incubated for 24 hrs by MTT assay
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[PMID: 37087895] |
| Calu-1 | IC50 |
0.3 μM
Compound: DC-2
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Antiproliferative activity against human Calu-1 cells assessed as reduction in cell viability incubated for 24 hrs by MTT assay
Antiproliferative activity against human Calu-1 cells assessed as reduction in cell viability incubated for 24 hrs by MTT assay
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[PMID: 37087895] |
| HEK-293T | IC50 |
1.1 μM
Compound: DC-2
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Cytotoxicity against HEK293T cells assessed as reduction in cell viability measured after 24 hrs by MTT assay
Cytotoxicity against HEK293T cells assessed as reduction in cell viability measured after 24 hrs by MTT assay
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[PMID: 37087895] |
| HT-1080 | IC50 |
0.1 μM
Compound: DC-2
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Antiproliferative activity against human HT-1080 cells assessed as reduction in cell viability incubated for 24 hrs by MTT assay
Antiproliferative activity against human HT-1080 cells assessed as reduction in cell viability incubated for 24 hrs by MTT assay
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[PMID: 37087895] |
In Vitro
PROTAC GPX4 degrader-1 (compound DC-2) (0.003-1 μM; 0.5-24 h) potently induces rapid, sustained, and concentration-dependent degradation of GPX4 in HT1080 cells, with a DC50 of 30 nM[1].
PROTAC GPX4 degrader-1 (10 μM; 24 h) induces ferroptosis in HT1080 cells, as the ferroptosis inhibitor Liproxstin-1 almost completely suppresses this cell death[1].
PROTAC GPX4 degrader-1 inhibits the proliferation of HT1080, Calu-1 and A375 cancer cells with IC50 values of 0.1 μM, 0.3 μM and 0.2 μM, respectively; it also exhibits low toxicity to normal HEK293T cells, with an IC50 of 1.1 μM[1].
PROTAC GPX4 degrader-1 (0.1 μM; 12 h) induces the degradation of GPX4 in HT1080 cells via the ubiquitin-proteasome pathway and the autophagy-lysosome pathway[1].
PROTAC GPX4 degrader-1 (0.3 μM; 1-12 h) induces sustained ROS accumulation in HT1080 cells, while the ferroptosis inhibitor Liproxstin-1 attenuates this effect[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:human fibrosarcoma HT1080 cells
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Concentration:0.003, 0.01, 0.03, 0.1, 0.3, 1 μM (concentration-dependent assay)
0.1 μM (time-dependent assay) -
Incubation Time:24 h (concentration-dependent assay)
0.5, 1, 2, 4, 6, 8, 12, 24 h (time-dependent assay) -
Result:Induced concentration-dependent GPX4 degradation with a DC50 of 30 nM, achieving near-complete depletion at 0.3 μM; a "hook" effect was observed at 1 μM.
Induced time-dependent degradation, depleting detectable GPX4 within 0.5 h, degrading over 80% of GPX4 within 12 h, and maintaining degradation activity for at least 24 h.
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Cell Line:human fibrosarcoma HT1080 cells
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Concentration:0.1 μM (PROTAC GPX4 degrader-1)
0.3 μM (MG132 (HY-13259)); 0.1 μM (Baf-A1 (HY-100558)); combination of MG132 and Baf-A1 -
Incubation Time:12 h (PROTAC GPX4 degrader-1 treatment)
2 h (pretreatment with inhibitors) -
Result:Partially blocked PROTAC GPX4 degrader-1-induced GPX4 degradation when cells were pretreated with MG132.
Partially blocked PROTAC GPX4 degrader-1-induced GPX4 degradation when cells were pretreated with Baf-A1.
Almost completely blocked PROTAC GPX4 degrader-1-induced GPX4 degradation when cells were pretreated with both inhibitors.
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Cell Line:human fibrosarcoma HT1080 cells
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Concentration:10 μM (PROTAC GPX4 degrader-1)
20 nM (Lip-1); 0.1 μM (Baf-A1) -
Incubation Time:24 h (PROTAC GPX4 degrader-1 treatment)
2 h (pretreatment with inhibitors) -
Result:Almost completely rescued cell death induced by PROTAC GPX4 degrader-1 when cells were pretreated with Lip-1.
Partially rescued cell death induced by PROTAC GPX4 degrader-1 when cells were pretreated with Baf-A1.
In Vivo
PROTAC GPX4 degrader-1 (5-40 mg/kg; intravenous injection; once every two days; for a total of 10 days) exhibits favorable safety in female Balb/c nude mice bearing HT1080 xenograft tumors, with no body weight loss observed[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Balb/c nude (female, 4 weeks old)[1]
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Dosage:20 mg/kg
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Administration:i.v.; single dose
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Result:Reduced GPX4 levels in tumor tissue within 6 h.
Achieved maximum GPX4 depletion within 12 h.
Maintained degradation activity for at least 48 h.
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Animal Model:Balb/c nude (female, 4 weeks old)[1]
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Dosage:5, 20, 40 mg/kg
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Administration:i.v.; once every two days; 10 days
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Result:Caused no observed weight loss.
Chemical Information
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CAS No. 2916433-81-1
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Appearance Solid
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Masse moléculaire 993.50
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Formule C50H57ClN10O10
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Color Light yellow to yellow
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SMILES
O=C(N1CCN(C(C2=CC=C(C=C2)OCC(N3CCC(CC3)CN4CCN(CCCNC5=CC=CC(C(N6C7C(NC(CC7)=O)=O)=O)=C5C6=O)CC4)=O)C8=CC=C(C=C8)Cl)CC1)C9=NOC(C)=C9[N+]([O-])=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
4°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Solvant et solubilité
In Vitro:
DMSO : 100 mg/mL (100.65 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (2.52 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (2.52 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocole
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ROS/oxidative-stress fluorescent staining
ROS/oxidative-stress fluorescent staining uses cell-permeant fluorogenic probes that become fluorescent after oxidation inside cells or tissues; commonly used examples include DCFH-DA/DCFDA for broad cellular oxidant detection, DHE for superoxide-related signal detection, MitoSOX for mitochondrial superoxide-related signal detection, and CellROX probes for oxidative-stress-associated fluorescence readouts. The assay detects probe oxidation rather than a single ROS species unless the probe and analysis method have been chemically validated for that species. DCFH-DA enters cells, is deacetylated by intracellular esterases to DCFH, and produces fluorescent DCF after oxidation, so the readout is used as an operational measure of total cellular oxidative stress rather than a species-specific ROS measurement. DHE and MitoSOX can report superoxide-related oxidation, but red fluorescence alone can include non-specific ethidium-like oxidation products; HPLC or optimized spectral approaches are
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Protocol for Cell Counting and Cell Density Analysis
Cell counting and cell-density analysis estimate the number of cells in a known volume or field area. Manual hemocytometer counting uses a chamber of defined geometry to convert counted cells into cells/mL, while automated counters and image-analysis workflows detect cell objects from optical, brightfield, fluorescence, impedance, or digital-image features. Trypan blue viability counting is based on dye exclusion: viable cells with intact membranes exclude dye, while non-viable cells with compromised membranes stain blue. The readout is total cell density, viable-cell density, dead-cell density, and percent viability. Cell density can also be estimated from microscopy images by counting objects per image area, from flow cytometry using calibrated volume or reference particles, or from in situ microscopy in bioreactors after calibration against reference methods such as hemocytometer or flow cytometry.
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Somatic Cell Culture
A method of simulating the in vivo environment in vitro to maintain the cell growth, differentation and main functions.
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CCK-8/WST-8 Cell Proliferation Assay
The CCK-8/WST-8 assay is based on the reduction of the water-soluble tetrazolium salt WST-8 to a water-soluble formazan product by cellular dehydrogenases in metabolically active cells, where the generated formazan amount is proportional to the number of living cells and is quantified by measuring absorbance in the visible range, providing a colorimetric readout for cell viability and proliferation assessment. This class of tetrazolium-based assays improves upon earlier MTT-based systems by producing a water-soluble formazan, eliminating the need for organic solubilization steps and enabling direct spectrophotometric measurement in culture medium.
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Ferroptosis Solutions
Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death characterized by lethal lipid peroxidation and sensitivity to suppression by iron chelators or lipophilic radical-trapping antioxidants. The core pathway links cystine uptake through system Xc−, glutathione availability, GPX4-dependent detoxification of phospholipid hydroperoxides, iron-dependent oxidative reactions, and polyunsaturated-phospholipid metabolism into a cell-death program that is biochemically and morphologically distinct from apoptosis, necrosis, and autophagy. The ferroptosis pathway is experimentally linked to phenotype through chemical and genetic perturbation. Erastin induces ferroptosis by inhibiting cystine uptake through system Xc− and weakening antioxidant defenses, while GPX4 inhibition or depletion causes lipid peroxide accumulation and ferroptotic cancer-cell death. ACSL4 and oxidizable arachidonoyl- or adrenoyl-containing phosphatidylethanolamines shape ferroptosis sensitivity by con
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Cell Counting-Based Growth Curve Assay
Cell counting-based growth curve assays quantify cell proliferation by directly measuring changes in viable cell number over time using manual or automated counting methods such as hemocytometer-based counting or instrument-assisted cell enumeration, enabling construction of growth curves that reflect population expansion dynamics in response to culture conditions. A widely used approach is trypan blue exclusion with hemocytometer counting, where membrane-compromised (non-viable) cells take up the dye, allowing discrimination between viable and non-viable cells while simultaneously enabling total cell number quantification. Repeated sampling across time points allows estimation of proliferation rate, growth phases, and comparative growth kinetics between experimental conditions.
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MTT Cell Proliferation Assay
The MTT assay is a colorimetric endpoint assay for estimating viable cell number, cell growth, cytotoxicity, or cell activation in cultured mammalian cells. Living cells reduce the yellow tetrazolium salt MTT into purple/blue formazan, while dead cells do not generate the same signal; the resulting color can be quantified with a multiwell spectrophotometer. MTT reduction is commonly interpreted as a readout of metabolic activity that often correlates with viable cell number, but it should not be treated as a direct cell-counting method unless the assay is optimized for the cell type and experimental condition. Studies show that MTT reduction can involve mitochondrial and non-mitochondrial reducing systems, and formazan may accumulate in intracellular lipid droplets rather than simply marking mitochondria.
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Pureté et documentation
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Fiche technique (277 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instruction de manipulation (2659 KB)
Références
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.0065 mL | 5.0327 mL | 10.0654 mL | 25.1636 mL |
| 5 mM | 0.2013 mL | 1.0065 mL | 2.0131 mL | 5.0327 mL | |
| 10 mM | 0.1007 mL | 0.5033 mL | 1.0065 mL | 2.5164 mL | |
| 15 mM | 0.0671 mL | 0.3355 mL | 0.6710 mL | 1.6776 mL | |
| 20 mM | 0.0503 mL | 0.2516 mL | 0.5033 mL | 1.2582 mL | |
| 25 mM | 0.0403 mL | 0.2013 mL | 0.4026 mL | 1.0065 mL | |
| 30 mM | 0.0336 mL | 0.1678 mL | 0.3355 mL | 0.8388 mL | |
| 40 mM | 0.0252 mL | 0.1258 mL | 0.2516 mL | 0.6291 mL | |
| 50 mM | 0.0201 mL | 0.1007 mL | 0.2013 mL | 0.5033 mL | |
| 60 mM | 0.0168 mL | 0.0839 mL | 0.1678 mL | 0.4194 mL | |
| 80 mM | 0.0126 mL | 0.0629 mL | 0.1258 mL | 0.3145 mL | |
| 100 mM | 0.0101 mL | 0.0503 mL | 0.1007 mL | 0.2516 mL |
PROTAC GPX4 degrader-1 Related Classifications
HY-149236 Related Classifications
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Keywords
- PROTAC GPX4 degrader-1
- 2916433-81-1
- PROTACs
- Glutathione Peroxidase
- Ferroptosis
- Reactive Oxygen Species (ROS)
- ubiquitin-proteasome pathway
- HEK293T cells
- non-small-cell lung cancer
- reactive oxygen species
- melanoma
- HT1080 cells
- ferroptosis
- autophagy-lysosome pathway
- glutathione peroxidase 4
- fibrosarcoma
- Inhibitor
- inhibitor
- inhibit