PROTAC GPX4 degrader-4
Based on 1 Customer Validation
PROTAC GPX4 degrader-4 is a potent GPX4 PROTAC degrader, with DC50 values of 1366.67 nM and 475.15 nM in T24 and RT4 cells, respectively. PROTAC GPX4 degrader-4 targets and degrades GPX4 protein via the ubiquitin-proteasome system, thereby inducing cellular ferroptosis. PROTAC GPX4 degrader-4 can be used for research on bladder cancer.
(Pink: GPX4 ligand (HY-N0193); Blue: Cereblon ligand (HY-103596); Black: linker (HY-W013907)).
For research use only. We do not sell to patients.
- Purity: 99.68%
- CAS No.: 3071165-43-7
- Formula: C43H58N2O13
- Molecular Weight:810.93
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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
Description
IC50 & Target
[1]|
GPX4 1366.67 nM (DC50, T24 cells) |
GPX4 475.15 nM (DC50, RT4 cells) |
In Vitro
PROTAC GPX4 degrader-4 (compound A7) (10-2560 nM; 600 s association time, 360 s dissociation time) binds to purified GPX4 protein with high affinity, with a Kd value of 5.32 nM[1].
PROTAC GPX4 degrader-4 (incubated for 30 min) directly binds to GPX4 in the lysate of human T24 bladder cancer cells and enhances the thermal stability of this protein[1].
PROTAC GPX4 degrader-4 (125-10000 nM; 1-48 h) effectively degrades GPX4 in a time- and concentration-dependent manner in human bladder cancer cell lines RT4 and T24, with DC50 values of 475.15 nM and 1366.67 nM, respectively[1].
PROTAC GPX4 degrader-4 (1-5 μM; 48 h) degrades GPX4 via the ubiquitin-proteasome system in human bladder cancer cell lines RT4 and T24, a process that requires simultaneous binding to both GPX4 and the CRBN E3 ligase[1].
PROTAC GPX4 degrader-4 (0.5-5 μM; 48 h) regulates GPX4 levels via a post-translational mechanism, as it does not alter GPX4 mRNA expression in RT4 and T24 human bladder cancer cells[1].
PROTAC GPX4 degrader-4 (incubated for 72 h) potently and selectively inhibits the proliferation of RT4, T24 and J82 human bladder cancer cells, with IC50 values of 0.09 μM, 2.97 μM and 7.58 μM, respectively, while exerting no obvious inhibitory effect on SV-HUC-1 normal cells[1].
PROTAC GPX4 degrader-4 (0.125-1 μM; 6-8 days) inhibits colony formation of human bladder cancer cell lines RT4 and T24 in a dose-dependent manner[1].
PROTAC GPX4 degrader-4 (0.5-2 μM; 48 h) significantly inhibits the migration of human bladder cancer RT4 and T24 cells[1].
PROTAC GPX4 degrader-4 (1-2 μM; 48 h) significantly inhibits the invasion of human bladder cancer T24 cells[1].
PROTAC GPX4 degrader-4 (0.5-5 μM; 48 h) increases the levels of intracellular lipid reactive oxygen species and total ROS, decreases GSH levels, and promotes MDA accumulation to induce ferroptosis in T24 and RT4 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:T24, RT4 human bladder cancer cells
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Concentration:1 μM (RT4 time-dependent); 5 μM (T24 time-dependent); 125, 250, 500, 1000, 2000, 4000 nM (RT4 concentration-dependent); 250, 500, 1000, 2000, 5000, 10000 nM (T24 concentration-dependent)
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Incubation Time:1-48 h (time-dependent); 48 h (concentration-dependent)
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Result:Induced time-dependent GPX4 degradation in both cell lines, with significant reduction in GPX4 protein levels observed after 4 h of treatment.
Induced concentration-dependent GPX4 degradation, with half-maximal degradation concentration (DC50) values of 475.15 nM in RT4 cells and 1366.67 nM in T24 cells.
Reached maximum degradation (Dmax) of 74.53% in RT4 cells and 78.29% in T24 cells.
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Cell Line:T24, RT4 human bladder cancer cells
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Concentration:1 μM (RT4 cells); 5 μM (T24 cells)
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Incubation Time:48 h (A7 treatment); 8 h (pretreatment)
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Result:MG-132 (HY-13259) reversed GPX4 degradation induced by PROTAC GPX4 degrader-4.
Pretreatment with CRBN ligand or arsenic trioxide partially inhibited GPX4 degradation, confirming that binding to both GPX4 and CRBN E3 ligase is required for the degrader's activity.
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Cell Line:T24, RT4 human bladder cancer cells
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Concentration:0.5, 1 μM (RT4 cells); 2, 5 μM (T24 cells)
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Incubation Time:48 h
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Result:Did not significantly affect GPX4 mRNA expression levels in either cell line compared to untreated controls.
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Cell Line:T24, RT4 human bladder cancer cells
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Concentration:0.125, 0.25, 0.5 μM (RT4 cells); 0.25, 0.5, 1 μM (T24 cells)
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Incubation Time:6-8 days
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Result:Dose-dependently inhibited colony formation in both cell lines, with greater inhibitory effects than ARS at equivalent concentrations.
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Cell Line:T24, RT4 human bladder cancer cells
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Concentration:0.5, 1 μM (RT4 cells); 1, 2 μM (T24 cells)
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Incubation Time:48 h
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Result:Significantly reduced wound closure in both cell lines compared to untreated controls, with greater inhibitory effects than ARS at equivalent concentrations.
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Cell Line:T24 human bladder cancer cells
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Concentration:1, 2 μM
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Incubation Time:48 h
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Result:Significantly reduced the number of invasive T24 cells compared to untreated controls, with greater inhibitory effects than ARS at equivalent concentrations.
In Vivo
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 mice (female; subcutaneous xenograft model)[1]
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Dosage:30 mg/kg; 60 mg/kg; 90 mg/kg
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Administration:i.p.; daily; 14 days
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Result:Achieved tumor growth inhibition (TGI) rates of 65.1%, 60.0%, and 85.6% for 30 mg/kg, 60 mg/kg, and 90 mg/kg dose groups respectively.
Showed no observable changes in mouse body weight across all dose groups.
Exhibited no significant hepatic or renal toxicity via H&E staining.
Revealed loosely arranged and reduced numbers of tumor cells via tumor tissue H&E staining.
Demonstrated significant reductions in Ki-67-positive tumor cells and GPX4 protein expression in tumor tissues via immunohistochemical staining.
Confirmed downregulated GPX4 protein levels in tumor tissues relative to controls via western blotting.
Chemical Information
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CAS No. 3071165-43-7
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Appearance Solid
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Molecular Weight 810.93
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Formula C43H58N2O13
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Color White to off-white
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SMILES
C[C@@H]1[C@@]2([H])[C@]34[C@](O[C@](OO3)(CC[C@@]4([H])[C@@H](CC2)C)C)([H])O[C@H]1OC(CCC(OCCCCCCCCCCCOC5=C6C(C(N(C7C(NC(CC7)=O)=O)C6=O)=O)=CC=C5)=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 101 mg/mL (124.55 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. 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. 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: ≥ 2.52 mg/mL (3.11 mM); Suspended solution
This protocol yields a suspended solution of ≥ 2.52 mg/mL (saturation unknown). Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.2 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.
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.
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 (280 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 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. 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 |
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| DMSO | 1 mM | 1.2332 mL | 6.1658 mL | 12.3315 mL | 30.8288 mL |
| 5 mM | 0.2466 mL | 1.2332 mL | 2.4663 mL | 6.1658 mL | |
| 10 mM | 0.1233 mL | 0.6166 mL | 1.2332 mL | 3.0829 mL | |
| 15 mM | 0.0822 mL | 0.4111 mL | 0.8221 mL | 2.0553 mL | |
| 20 mM | 0.0617 mL | 0.3083 mL | 0.6166 mL | 1.5414 mL | |
| 25 mM | 0.0493 mL | 0.2466 mL | 0.4933 mL | 1.2332 mL | |
| 30 mM | 0.0411 mL | 0.2055 mL | 0.4111 mL | 1.0276 mL | |
| 40 mM | 0.0308 mL | 0.1541 mL | 0.3083 mL | 0.7707 mL | |
| 50 mM | 0.0247 mL | 0.1233 mL | 0.2466 mL | 0.6166 mL | |
| 60 mM | 0.0206 mL | 0.1028 mL | 0.2055 mL | 0.5138 mL | |
| 80 mM | 0.0154 mL | 0.0771 mL | 0.1541 mL | 0.3854 mL | |
| 100 mM | 0.0123 mL | 0.0617 mL | 0.1233 mL | 0.3083 mL |
PROTAC GPX4 degrader-4 Related Classifications
HY-174086 Related Classifications
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Keywords
- PROTAC GPX4 degrader-4
- 3071165-43-7
- PROTACs
- Glutathione Peroxidase
- Ferroptosis
- ROS Kinase
- Glutathione peroxidase 4
- Bladder cancer cells
- Ubiquitin-proteasome system
- T24 human bladder cancer cells
- J82 human bladder cancer cells
- CRBN E3 ligase
- RT4 human bladder cancer cells
- GPX4
- SV-HUC-1 normal cells
- Inhibitor
- inhibitor
- inhibit