Art. -Nr.: HY-174458

MD-4251

Name: MD-4251
Brand: MedChemExpress
SKU: HY-174458
Price: 355.00 USD
Availability: InStock
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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).

Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.

Reinheit : 98.03%
Formel: C₄₇H₅₃Cl₂FN₈O₄
Molecular Weight:883.88

Speicherung:

-20°C, protect from light

* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

MD-4251 Chemical Structure

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Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

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^[1]^[2]. (Pink: MDM2 ligand (HY-130684); Blue: Cereblon ligand (HY-W883326); Black: linker).

IC₅₀ & Target

^[1]^[2]

MDM2

0.2 nM (DC₅₀)

p53

DSC1

NBEA

CASP14

Alle PROTACs Isoform-spezifische Produkte anzeigen :

In Vitro

Anti-cancerOthers

Anti-cancer

MD-4251 potently inhibits the growth of wild-type p53 acute leukemia cell lines RS4;11 (IC₅₀ = 1 nM), MV4;11 (IC₅₀ = 2 nM), and MOLM-13 (IC₅₀ = 2 nM), while showing minimal activity against the mutated p53 cell line RS4;11/IRMI2 (IC₅₀ > 1000 nM)^[1].
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 D_max 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].

Others

MD-4251 exhibits excellent metabolic stability in liver microsomes and plasma from multiple species, with a half-life exceeding 60 min across all tested samples^[1].
MD-4251 (1 μM; Up to 60 min) demonstrates excellent microsomal and plasma stability (T_1/2 >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.

Western Blot Analysis^[2]

Cell Line:

RS4;11 human acute leukemia cell line (wild-type p53)
Concentration:

0.03-300 nM
Incubation Time:

2 h
Result:

Induced potent MDM2 degradation with a DC₅₀ of 0.2 nM and a maximum degradation (D_MAX) 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.

Cell Proliferation Assay^[2]

Cell Line:

RS4;11 human acute leukemia cell line (wild-type p53)
Concentration:

Serial dilutions
Incubation Time:

4 days
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.

Cell Proliferation Assay^[2]

Cell Line:

MV4;11 human acute leukemia cell line (wild-type p53)
Concentration:

Serial dilutions
Incubation Time:

4 days
Result:

Potently inhibited MV4;11 cell growth with an IC₅₀ of 2 nM.

Cell Proliferation Assay^[2]

Cell Line:

MOLM-13 human acute leukemia cell line (wild-type p53)
Concentration:

Serial dilutions
Incubation Time:

4 days
Result:

Potently inhibited MOLM-13 cell growth with an IC₅₀ of 2 nM.

Parmacokinetics

Species	Dose	Route	CL	V_ss	T_1/2	C_max	AUC_0-24	F
Mice^[2]	1 mg/kg	i.v.	0.6 mL/min/kg	0.9 L/kg	/	/	/	/
Mice^[2]	3 mg/kg	p.o.	/	/	>24 h	1157 ng/mL	20658 ng·h/mL	39 %

In Vivo

Anti-cancerApoptosisOthers

Anti-cancer

MD-4251 (3-50 mg/kg; p.o.; three times a week, once weekly, single dose; 3 weeks) induces dose- and schedule-dependent tumor growth inhibition in RS4;11 xenografts, with a single 50 mg/kg oral dose achieving long-lasting complete tumor regression in female SCID mice^[2].

Anti-cancer

Apoptosis

MD-4251 (10-30 mg/kg; p.o.; single dose) induces sustained MDM2 depletion and p53 pathway activation in RS4;11 xenograft tumors in female SCID mice, with effects persisting for at least 72 hours at a 30 mg/kg dose^[2].

Others

MD-4251 (60 mg/kg; p.o.; single dose) does not induce thrombocytopenia in female BALB/c mice^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

SCID (female)^[2]
Dosage:

3 mg/kg (3x/week); 3 mg/kg (1x/week); 10 mg/kg (1x/week); 50 mg/kg (single dose)
Administration:

p.o.; three times a week; 3 weeks; p.o.; once weekly; 3 weeks; p.o.; single dose
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.

Animal Model:

SCID (female)^[2]
Dosage:

10 mg/kg; 30 mg/kg
Administration:

p.o.; single dose
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.

Animal Model:

BALB/c (female)^[2]
Dosage:

60 mg/kg
Administration:

p.o.; single dose
Result:

Did not significantly reduce platelet counts compared to control treatment.

Related Protocols :

Chemical Information

Appearance Solid
Molecular Weight 883.88
Formel C₄₇H₅₃Cl₂FN₈O₄
Color White to off-white
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
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

-20°C, protect from light

* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

Lösungsmittel & Löslichkeit

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.1314 mL

5.6569 mL

11.3138 mL

5 mM

0.2263 mL

1.1314 mL

2.2628 mL

10 mM

0.1131 mL

0.5657 mL

1.1314 mL

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.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

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.

Protocol 1

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.

Protocol 2

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.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (2.83 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
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

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (285 KB)
SDS (252 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[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]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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

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MD-4251

Alle PROTACs Isoform-spezifische Produkte anzeigen