MD-4251
Based on 1 Customer Validation
MD-4251 is an orally active MDM2 PROTAC degrader with a DC50 of 0.2 nM in RS4;11 cells. MD-4251 induces cereblon-dependent depletion and degradation of MDM2 protein, elevates p53 protein levels and activates p53. MD-4251 inhibits the proliferation of wild-type p53 acute leukemia cells, induces complete and durable tumor regression in xenograft models, and upregulates the protein levels of DSC1, NBEA and CASP14. MD-4251 can be used in studies related to acute leukemia.
(Pink: MDM2 ligand (HY-130684); Blue: Cereblon ligand (HY-W883326); Black: linker).
연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.
- Purity : 98.03%
- 화학식: C47H53Cl2FN8O4
- 분자량:883.88
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보관:
-20°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
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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용액&용해도
- Protocol
- 순도&문서
- References
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Help & FAQs
All PROTACs Isoforms
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Biological Activity
제품 설명
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MDM2 0.2 nM (DC50) |
p53 |
DSC1 |
NBEA |
CASP14 |
In Vitro
MD-4251 (≥3 nM; 2 h) degrades MDM2 in RS4;11 cells with a DC50 of 0.2 nM and 96% maximal degradation within 2 h, while increasing p53 protein levels by over 6-fold at concentrations of 3 nM or higher[1].
MD-4251 upregulates p53, DSC1, NBEA, and CASP14 protein levels in MV4;11 and MOLM-13 cells, with no detectable MDM2 depletion due to low baseline MDM2 expression[1].
MD-4251 (0.03-300 nM; 2 h) potently degrades MDM2 with a DC50 of 0.2 nM and Dmax of 96% in RS4;11 cells after 2 h, accompanied by robust p53 upregulation, while showing minimal effects on other cereblon neo-substrates[2].
MD-4251 (Serial dilutions; 4 days) inhibits RS4;11 cell growth with an IC50 of 1 nM, and this activity is dependent on cereblon binding[2].
MD-4251 (Serial dilutions; 4 days) inhibits MV4;11 cell growth with an IC50 of 2 nM[2].
MD-4251 (Serial dilutions; 4 days) inhibits MOLM-13 cell growth with an IC50 of 2 nM[2].
MD-4251 (3 nM; 2 h) upregulates p53 and three additional proteins (DSC1, NBEA, CASP14) in RS4;11 cells, with no protein depleted by more than 2-fold[2].
MD-4251 (1 μM; Up to 60 min) demonstrates excellent microsomal and plasma stability (T1/2 >60 min) in human, mouse, rat, dog, and monkey samples[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:RS4;11 human acute leukemia cell line (wild-type p53)
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Concentration:0.03-300 nM
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Incubation Time:2 h
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Result:Induced potent MDM2 degradation with a DC50 of 0.2 nM and a maximum degradation (DMAX) of 96% at 2 h.
Depleted MDM2 protein by >70% at 0.3 nM.
Increased p53 protein levels by >6-fold at 3 nM or higher concentrations.
Reduced MDM2 degradation at concentrations ≥100 nM, while p53 upregulation remained robust.
Showed no effect on GSPT1 or IKZF3 levels.
Exerted only a modest effect on IKZF1 and CK1α levels.
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Cell Line:RS4;11 human acute leukemia cell line (wild-type p53)
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Concentration:Serial dilutions
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Incubation Time:4 days
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Result:Potently inhibited RS4;11 cell growth with an IC50 of 1 nM.
Lost cell growth inhibition activity (IC50 >100 nM) when co-treated with 10 μM of the cereblon ligand RKA-4237.
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Cell Line:MV4;11 human acute leukemia cell line (wild-type p53)
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Concentration:Serial dilutions
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Incubation Time:4 days
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Result:Potently inhibited MV4;11 cell growth with an IC50 of 2 nM.
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Cell Line:MOLM-13 human acute leukemia cell line (wild-type p53)
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Concentration:Serial dilutions
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Incubation Time:4 days
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Result:Potently inhibited MOLM-13 cell growth with an IC50 of 2 nM.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SCID (female)[2]
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Dosage:3 mg/kg (3x/week); 3 mg/kg (1x/week); 10 mg/kg (1x/week); 50 mg/kg (single dose)
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Administration:p.o.; three times a week; 3 weeks; p.o.; once weekly; 3 weeks; p.o.; single dose
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Result:Inhibited tumor growth by 91% at 3 mg/kg three times weekly and 10 mg/kg once weekly at the end of the 3-week treatment period.
Inhibited tumor growth by 53% at 3 mg/kg once weekly at the end of the 3-week treatment period.
Induced rapid and complete tumor regression with a single oral dose of 50 mg/kg, with no detectable tumors remaining in all mice 24 days after regression was achieved.
Caused no significant weight loss or other signs of toxicity across all doses.
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Animal Model:SCID (female)[2]
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Dosage:10 mg/kg; 30 mg/kg
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Administration:p.o.; single dose
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Result:Depleted MDM2 protein to 35% and 29% of vehicle control levels in tumor tissue at 6 and 24 hours post 10 mg/kg single oral dose, respectively.
Increased p53 protein to 179% of control at 24 hours post 10 mg/kg single oral dose.
Increased cleaved PARP to 235% of control at 24 hours post 10 mg/kg single oral dose.
Induced sustained MDM2 depletion at 24, 48, and 72 hours post 30 mg/kg single oral dose, accompanied by robust increases in p53 and PUMA protein levels in tumor tissue.
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Animal Model:BALB/c (female)[2]
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Dosage:60 mg/kg
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Administration:p.o.; single dose
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Result:Did not significantly reduce platelet counts compared to control treatment.
Chemical Information
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Appearance Solid
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분자량 883.88
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화학식 C47H53Cl2FN8O4
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Color White to off-white
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SMILES
O=C1NC2=CC(Cl)=CC=C2[C@]13C4(CCCCC4)N[C@H]([C@@H]3C5=CC=CC(Cl)=C5F)C(N[C@@H]6CC[C@H](CC6)CN7CCN(CC7)C8=CC=C9C(N(N=C9C%10C(NC(CC%10)=O)=O)C)=C8)=O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
-20°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
용액&용해도
In Vitro:
DMSO : 100 mg/mL (113.14 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 (protect from light). 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 (protect from light). 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 (2.83 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 (2.83 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 (protect from light)
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.
순도&문서
References
[1]. Wu S, et al. MDM2 Degrader as a Promising Therapeutic Strategy for Cancer Treatment. Journal of medicinal chemistry. 2025 Jul 10;68(13):13246-13248. [Content Brief]
[2]. Acharyya RK, et al. MD-4251: A First-in-Class Oral MDM2 Degrader Inducing Complete Tumor Regression with Single-Dose Administration. Journal of medicinal chemistry. 2025 Jul 10;68(13):13249-13267. [Content Brief]
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 (protect from light). 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 | 1.1314 mL | 5.6569 mL | 11.3138 mL | 28.2844 mL |
| 5 mM | 0.2263 mL | 1.1314 mL | 2.2628 mL | 5.6569 mL | |
| 10 mM | 0.1131 mL | 0.5657 mL | 1.1314 mL | 2.8284 mL | |
| 15 mM | 0.0754 mL | 0.3771 mL | 0.7543 mL | 1.8856 mL | |
| 20 mM | 0.0566 mL | 0.2828 mL | 0.5657 mL | 1.4142 mL | |
| 25 mM | 0.0453 mL | 0.2263 mL | 0.4526 mL | 1.1314 mL | |
| 30 mM | 0.0377 mL | 0.1886 mL | 0.3771 mL | 0.9428 mL | |
| 40 mM | 0.0283 mL | 0.1414 mL | 0.2828 mL | 0.7071 mL | |
| 50 mM | 0.0226 mL | 0.1131 mL | 0.2263 mL | 0.5657 mL | |
| 60 mM | 0.0189 mL | 0.0943 mL | 0.1886 mL | 0.4714 mL | |
| 80 mM | 0.0141 mL | 0.0707 mL | 0.1414 mL | 0.3536 mL | |
| 100 mM | 0.0113 mL | 0.0566 mL | 0.1131 mL | 0.2828 mL |
MD-4251 Related Classifications
HY-174458 Related Classifications
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