Cat. No.: HY-114312

MD-224

8 Cited Publications

Customer Review

Based on 8 publication(s) in Google Scholar

MD-224 is a first-in-class and highly potent small-molecule human murine double minute 2 (MDM2) degrader based on the proteolysistargeting chimera (PROTAC) concept. MD-224 consists of ligands for Cereblon and MDM2. MD-224 induces rapid degradation of MDM2 at concentrations <1 nM in human leukemia cells, and achieves an IC₅₀ value of 1.5 nM in inhibition of growth of RS4;11 cells. MD-224 has the potential to be a new class of anticancer agent. MD-224 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
(Pink: MDM-2/p53 ligand (HY-125858); Blue: Cereblon ligand (HY-43722); Black: linker).

For research use only. We do not sell to patients.

Purity: 99.60%
CAS No.: 2136247-12-4
Formula: C₄₈H₄₃Cl₂FN₆O₆
Molecular Weight:889.80

Storage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

MD-224 Chemical Structure

CAS No.: 2136247-12-4

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Top Publications Citing

Use of MCE Products

Fluorescent Dye

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

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
Chemical Information
Publications (8)
Solvent & Solubility
- In Vitro
Purity & Documentation
References
Help & FAQs
Bioz

Biological Activity

Description

MD-224 is a first-in-class and highly potent small-molecule human murine double minute 2 (MDM2) degrader based on the proteolysistargeting chimera (PROTAC) concept. MD-224 consists of ligands for Cereblon and MDM2. MD-224 induces rapid degradation of MDM2 at concentrations <1 nM in human leukemia cells, and achieves an IC₅₀ value of 1.5 nM in inhibition of growth of RS4;11 cells. MD-224 has the potential to be a new class of anticancer agent^[1]. MD-224 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups. (Pink: MDM-2/p53 ligand (HY-125858); Blue: Cereblon ligand (HY-43722); Black: linker).

IC₅₀ & Target^[1]

MDM2

1 nM (IC₅₀)

All PROTACs Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
KG-1	IC₅₀	>10 μM Compound: 14; MD-224	Inhibition of cell growth in human KG-1 cells harbouring mutant p53 incubated for 4 days by lactate dehydrogenase-based WST-8 assay Inhibition of cell growth in human KG-1 cells harbouring mutant p53 incubated for 4 days by lactate dehydrogenase-based WST-8 assay	[PMID: 30525597]
ML-2	IC₅₀	4.4 μM Compound: 14; MD-224	Inhibition of cell growth in human ML-2 cells harbouring wild-type p53 incubated for 4 days by lactate dehydrogenase-based WST-8 assay Inhibition of cell growth in human ML-2 cells harbouring wild-type p53 incubated for 4 days by lactate dehydrogenase-based WST-8 assay	[PMID: 30525597]
MOLM-13	IC₅₀	7.3 μM Compound: 14; MD-224	Inhibition of cell growth in human MOLM-13 cells harbouring wild-type p53 incubated for 4 days by lactate dehydrogenase-based WST-8 assay Inhibition of cell growth in human MOLM-13 cells harbouring wild-type p53 incubated for 4 days by lactate dehydrogenase-based WST-8 assay	[PMID: 30525597]
MOLM-14	IC₅₀	10.5 μM Compound: 14; MD-224	Inhibition of cell growth in human MOLM-14 cells harbouring wild-type p53 incubated for 4 days by lactate dehydrogenase-based WST-8 assay Inhibition of cell growth in human MOLM-14 cells harbouring wild-type p53 incubated for 4 days by lactate dehydrogenase-based WST-8 assay	[PMID: 30525597]
MONO-MAC-6	IC₅₀	>10 μM Compound: 14; MD-224	Inhibition of cell growth in human MONO-MAC-6 cells harbouring mutant p53 incubated for 4 days by lactate dehydrogenase-based WST-8 assay Inhibition of cell growth in human MONO-MAC-6 cells harbouring mutant p53 incubated for 4 days by lactate dehydrogenase-based WST-8 assay	[PMID: 30525597]
OCI-AML-5	IC₅₀	33.1 μM Compound: 14; MD-224	Inhibition of cell growth in human OCI-AML5 cells harbouring wild-type p53 incubated for 4 days by lactate dehydrogenase-based WST-8 assay Inhibition of cell growth in human OCI-AML5 cells harbouring wild-type p53 incubated for 4 days by lactate dehydrogenase-based WST-8 assay	[PMID: 30525597]
RS4-11	IC₅₀	1.5 nM Compound: 14; MD-224	Inhibition of cell growth in human RS4-11 cells incubated for 4 days by Lactate dehydrogenase based WST-8 assay Inhibition of cell growth in human RS4-11 cells incubated for 4 days by Lactate dehydrogenase based WST-8 assay	[PMID: 30525597]
SIG-M5	IC₅₀	19.8 μM Compound: 14; MD-224	Inhibition of cell growth in human SIG-M5 cells harbouring wild-type p53 incubated for 4 days by lactate dehydrogenase-based WST-8 assay Inhibition of cell growth in human SIG-M5 cells harbouring wild-type p53 incubated for 4 days by lactate dehydrogenase-based WST-8 assay	[PMID: 30525597]

In Vitro

MD-224 (1-30 nM; 2 hours) effectively induces depletion of MDM2 protein and concurrently accumulation of p53 protein in a dose-dependent manner in RS4;11 cells^[1].
MD-224 (30 nM; 6 hours) is more potent than MI-1061 in induction of transcriptional upregulation of these p53 target genes but have no effect on TP53 itself in RS4;11 cells^[1].
MD-224 (0.001-1 μM; 24 hours) induces robust apoptosis at ≤10 nM in a dose-dependent manner upon a 24 hours treatment^[1].

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

Western Blot Analysis^[1]

Cell Line:

RS4;11 cells
Concentration:

1 nM; 3 nM; 10 nM; 30 nM
Incubation Time:

2 hours
Result:

Decreased MDM2 protein and accumulated of p53 protein.

RT-PCR^[1]

Cell Line:

RS4;11 cells
Concentration:

30 nM
Incubation Time:

6 hours
Result:

Upregulated p53 target gene expression.

Apoptosis Analysis^[1]

Cell Line:

RS4;11 cells
Concentration:

0.001 μM, 0.003 μM, 0.01 μM, 0.03 μM, 0.1 μM, 0.3 μM, 1 μM
Incubation Time:

24 hours
Result:

Induces robust apoptosis in RS4;11 cells.

Chemical Information

CAS No. 2136247-12-4
Appearance Solid
Molecular Weight 889.80
Formula C₄₈H₄₃Cl₂FN₆O₆
Color Off-white to yellow
SMILES

FC1=C(Cl)C=CC=C1[C@@H]2[C@@]3(C(C=CC(Cl)=C4)=C4NC3=O)C5(CCCCC5)N[C@H]2C(NC6=CC=C(C(NCCCC#CC7=C(CN(C8C(NC(CC8)=O)=O)C9=O)C9=CC=C7)=O)C=C6)=O
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Publications (8)

All WBBio/Physico-chemical AssayOthers

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Journal Impact Factor

Nat Commun

Human iPSC-based Modeling of Pulmonary Fibrosis Reveals p300/CBP Inhibition Suppresses Alveolar Transitional Cell State. [Abstract]

2026 Feb 12;17(1):1214. PMID: 41680175
Cell Rep

MDM2 binds and ubiquitinates PARP1 to enhance DNA replication fork progression. [Abstract]

2022 May 31;39(9):110879. PMID: 35649362

MD-224 purchased from MedChemExpress. Usage Cited in: Cell Rep. 2022 May 31;39(9):110879. [Abstract]

Immunoblot analysis of SJSA-1 cells treated with MDM2-binding compounds (Nutlin, 20 μM; MI-1061, 1 μM) or the MDM2 PROTAC (MD-224, 1 μM) for 12 h. MD-224 induced p53-activation comparable with MI1061, as shown by p21 accumulation but depleted MDM2.

MD-224 purchased from MedChemExpress. Usage Cited in: Cell Rep. 2022 May 31;39(9):110879. [Abstract]

Confirming comparable p53 activation by MI-1061, MD-224, and Nutlin, as shown by p21 accumulation, whereas MD-224 specifically depleted MDM2.

MD-224 purchased from MedChemExpress. Usage Cited in: Cell Rep. 2022 May 31;39(9):110879. [Abstract]

Treatment scheme. SJSA-1 cells were treated with Nutlin (20 μM, 6 h), MI-1061 (1 μM, 6 h), MD-224 (1 μM, 6 h), and the PARPi olaparib (10 μM, 12 h). DNA fiber assays were performed, sequentially labeling newly synthetized DNA with 5-chloro-2-deoxyuridine (CldU; 25 μM, 20 min) and 5-iodo-2-deoxyuridine (IdU) (25 μM, 60 min).

MD-224 purchased from MedChemExpress. Usage Cited in: Cell Rep. 2022 May 31;39(9):110879. [Abstract]

RPE cells were treated with 1 μM MDM2 PROTAC (MD-224), 1 μM MI-1061 (ligand control), or 10 μM Nutlin for 48 h to reveal MDM2-dependent loss of PARP1.

MD-224 purchased from MedChemExpress. Usage Cited in: Cell Rep. 2022 May 31;39(9):110879. [Abstract]

SJSA-1 cells were treated with 1 μM MDM2 PROTAC (MD-224), 1 μM MI-1061 (ligand control), or 20 μM Nutlin for 12 h, followed by immunoblot analysis. Treatment with MD-224 induced a p53 response comparable with MI-1061, as shown by p21 levels, leading to MDM2 degradation.
Anal Chem

Hydrogen/Deuterium Exchange for Chiral Stability Assessment in Acidic Methine-Containing Compounds. [Abstract]

2025 Dec 2;97(47):26097-26107. PMID: 41243541

MD-224 purchased from MedChemExpress. Usage Cited in: Anal Chem. 2025 Dec 2;97(47):26097-26107. [Abstract]

Calculated Acidic Methine pKa, and Measured Half-Lives for PROTACs at 37℃ in 0.1 M Phosphate Buffer (D2O, pD 7.8).(MD-224 (compound 25))
Structure

PROTAC-mediated activation, rather than degradation, of a nuclear receptor reveals complex ligand-receptor interaction network. [Abstract]

2024 Dec 5;32(12):2352-2363.e8. PMID: 39389062
University of Wisconsin

2025.
bioRxiv

2023 May 26.
Research Square Print

November 18th, 2022
St

Johns University. 2021 Jul.

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (112.38 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

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Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.1238 mL

5.6192 mL

11.2385 mL

5 mM

0.2248 mL

1.1238 mL

2.2477 mL

10 mM

0.1124 mL

0.5619 mL

1.1238 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator

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

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Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (275 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 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)

References

[1]. Li Y, et al. Discovery of MD-224 as a First-in-Class, Highly Potent, and Efficacious Proteolysis TargetingChimera Murine Double Minute 2 Degrader Capable of Achieving Complete and Durable TumorRegression. J Med Chem. 2019 Jan 24;62(2):448-466 [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

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	1.1238 mL	5.6192 mL	11.2385 mL	28.0962 mL
	5 mM	0.2248 mL	1.1238 mL	2.2477 mL	5.6192 mL
	10 mM	0.1124 mL	0.5619 mL	1.1238 mL	2.8096 mL
	15 mM	0.0749 mL	0.3746 mL	0.7492 mL	1.8731 mL
	20 mM	0.0562 mL	0.2810 mL	0.5619 mL	1.4048 mL
	25 mM	0.0450 mL	0.2248 mL	0.4495 mL	1.1238 mL
	30 mM	0.0375 mL	0.1873 mL	0.3746 mL	0.9365 mL
	40 mM	0.0281 mL	0.1405 mL	0.2810 mL	0.7024 mL
	50 mM	0.0225 mL	0.1124 mL	0.2248 mL	0.5619 mL
	60 mM	0.0187 mL	0.0937 mL	0.1873 mL	0.4683 mL
	80 mM	0.0140 mL	0.0702 mL	0.1405 mL	0.3512 mL
	100 mM	0.0112 mL	0.0562 mL	0.1124 mL	0.2810 mL

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MD-224

Apoptosis Compound Library

Metabolism/Protease Compound Library

Anti-Cancer Compound Library

Autophagy Compound Library

Anti-Aging Compound Library

Oxygen Sensing Compound Library

Ubiquitination Compound Library

Ferroptosis Compound Library

Pyroptosis Compound Library

Chemical Probe Library

Glutamine Metabolism Compound Library

Anti-Pancreatic Cancer Compound Library

Anti-Blood Cancer Compound Library

Anti-Cancer Metabolism Compound Library

Transcription Factor-Targeted Library

Anti-Liver Cancer Compound Library

Anti-Colorectal Cancer Compound Library

Heterocyclic Compound Library

Metabolic Enzyme Compound Library

PROTAC Library

Highly Selective Inhibitors Library

Anti-Hematopathy Compound Library

Anti-Ovarian Cancer Compound Library

Multi-Target Compound Library

Mitophagy Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

Amino Acid Metabolism Compound Library

Cell Proliferation Compound Library

High-Throughput Bioactive Compound Library

Posttranslational Modification Library

Alkyne Compound Library

Publications Citing Use of MedChemExpress (MCE) MD-224

All PROTACs Isoforms

Biological Activity

Chemical Information

Publications (8)

Solvent & Solubility

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

MD-224 Related Classifications

Cat. No.: HY-114312