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)).
For research use only. We do not sell to patients.
- Purity: 98.53%
- CAS No.: 2916433-81-1
- Formula: C50H57ClN10O10
- Molecular Weight:993.50
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Storage:
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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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
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GPX4 30 nM (DC50) |
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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] |
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.
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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.
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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Molecular Weight 993.50
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Formula 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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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Solvent & Solubility
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)
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.
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.
Purity & Documentation
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Data Sheet (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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Handling Instructions (2659 KB)
References
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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- 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