DeFer-2
Based on 1 Customer Validation
DeFer-2 is a Ferritin PROTAC degrader with a Kd value of 17.1 μM. DeFer-2 recruits the VHL E3 ligase to induce targeted degradation of ferritin via the ubiquitin-proteasome system, triggers iron overload stress in cancer cells, and further activates caspase 3-GSDME-mediated pyroptosis through massive ROS production. DeFer-2 can be used for research related to melanoma.
(Pink: Ferritin ligand (HY-N1446); Blue: VHL ligand (HY-125845); Black: linker (HY-N0067)).
For research use only. We do not sell to patients.
- Purity: 98.25%
- CAS No.: 3058911-16-0
- Formula: C44H69N5O5S
- Molecular Weight:780.11
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Storage:
-20°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
Biological Activity
Description
IC50 & Target
[1]|
Caspase 3 |
VHL |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| B16-F10 | IC50 |
3.1 μM
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Cytotoxicity against mouse B16F10 melanoma cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay.
Cytotoxicity against mouse B16F10 melanoma cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay.
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37094179 |
| B16-F10 | IC50 |
1.5 μM
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Cytotoxicity against mouse B16F10 melanoma cells assessed as reduction in cell viability incubated for 48 hrs by CCK-8 assay.
Cytotoxicity against mouse B16F10 melanoma cells assessed as reduction in cell viability incubated for 48 hrs by CCK-8 assay.
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37094179 |
In Vitro
DeFer-2 (0.5 μM; 8-12 h) significantly reduces the abundance of ferritin and multiple mitochondria-related proteins, and markedly increases the levels of intracellular free iron ions and reactive oxygen species (ROS) in B16F10 cells[1].
DeFer-2 (5 μM; 24 h) induces pyroptotic morphological features and LDH release in B16F10 cells, and its co-administration with 25 μM DFOM (HY-B0988) significantly inhibits cell death[1].
DeFer-2 (1-10 μM; 8-20 h) dose-dependently increases the levels of cleaved caspase 3 (8 h) and GSDME-N (20 h) in B16F10 cells, and this effect is attenuated by pretreatment with 10 mM GSH (HY-D0187)[1].
Combination treatment with DeFer-2 (5 μM; 24 h) and either 10 μM Z-VAD (HY-164388) or 0.1 μM NSCI significantly reduces cell death and LDH release in B16F10 cells, whereas co-treatment with 10 μM VX-765 (HY-13205) does not alter cell death[1].
DeFer-2 (0.001-10 μM; 24-48 h) induces significant cytotoxicity in B16F10 cells, with IC50 values of 3.1 μM and 1.5 μM at 24 h and 48 h, respectively[1].
DeFer-2 (0.008-5 μM; 4-24 h) degrades ferritin in a time- and concentration-dependent manner in B16F10 cells[1].
DeFer-2 binds to ferritin with relatively low but acceptable affinity, with a Kd of 17.1 μM at 30°C[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:B16F10 melanoma cells
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Concentration:0.008, 0.04, 0.2, 0.5, 1, 5 μM
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Incubation Time:4, 8, 12, 16, 24 h
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Result:Induced ferritin degradation in a time- and dose-dependent manner.
Reached maximum degradation potency at 12 h, achieving a maximum degradation rate of 58% at 5 μM.
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Cell Line:B16F10 melanoma cells
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Concentration:1, 5, 10 μM
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Incubation Time:8, 20 h
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Result:Elevated the expression levels of cleaved caspase 3 (8 h) and GSDME-N (20 h) in a dose-dependent manner, and this effect was attenuated by pretreatment with 10 mM GSH, confirming the critical role of ROS in the caspase 3-GSDME pyroptosis pathway triggered by the product.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (8-week-old male, melanoma model via B16F10 cell flank injection)[1]
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Dosage:10 mg/kg
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Administration:i.v.; every other day; 4 total doses; 15 days
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Result:Inhibited tumor growth compared to albumin vehicle saline control.
Improved survival compared to albumin vehicle saline control.
Chemical Information
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CAS No. 3058911-16-0
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Appearance Solid
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Molecular Weight 780.11
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Formula C44H69N5O5S
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Color Off-white to light yellow
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SMILES
CC1=C(SC=N1)C2=CC=C(C=C2)CNC([C@H](C[C@@H](O)C3)N3C([C@H](C(C)(C)C)NC(CCCNC(CCCCCCC/C=C\CCCCCCCC)=O)=O)=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (128.19 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 (3.20 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 (3.20 mM); Suspended solution
This protocol yields a suspended solution of ≥ 2.5 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 (25.0 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.
Purity & Documentation
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Data Sheet (280 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 | 1.2819 mL | 6.4094 mL | 12.8187 mL | 32.0468 mL |
| 5 mM | 0.2564 mL | 1.2819 mL | 2.5637 mL | 6.4094 mL | |
| 10 mM | 0.1282 mL | 0.6409 mL | 1.2819 mL | 3.2047 mL | |
| 15 mM | 0.0855 mL | 0.4273 mL | 0.8546 mL | 2.1365 mL | |
| 20 mM | 0.0641 mL | 0.3205 mL | 0.6409 mL | 1.6023 mL | |
| 25 mM | 0.0513 mL | 0.2564 mL | 0.5127 mL | 1.2819 mL | |
| 30 mM | 0.0427 mL | 0.2136 mL | 0.4273 mL | 1.0682 mL | |
| 40 mM | 0.0320 mL | 0.1602 mL | 0.3205 mL | 0.8012 mL | |
| 50 mM | 0.0256 mL | 0.1282 mL | 0.2564 mL | 0.6409 mL | |
| 60 mM | 0.0214 mL | 0.1068 mL | 0.2136 mL | 0.5341 mL | |
| 80 mM | 0.0160 mL | 0.0801 mL | 0.1602 mL | 0.4006 mL | |
| 100 mM | 0.0128 mL | 0.0641 mL | 0.1282 mL | 0.3205 mL |
DeFer-2 Related Classifications
HY-175381 Related Classifications
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