MD-224

Name: MD-224
Brand: MedChemExpress
SKU: HY-114312
Rating: 5.0 (6 reviews)

Cat. No.: HY-114312 Purity: 99.60%: Data Sheet
COA

SDS
Handling Instructions
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Technical Support

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.

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

MD-224 Chemical Structure

CAS No. : 2136247-12-4

Size	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	In-stock	Estimated Time of Arrival: December 31
10 mg	In-stock	Estimated Time of Arrival: December 31
25 mg	In-stock	Estimated Time of Arrival: December 31
50 mg	In-stock	Estimated Time of Arrival: December 31
100 mg	In-stock	Estimated Time of Arrival: December 31
250 mg	In-stock	Estimated Time of Arrival: December 31
500 mg	In-stock	Estimated Time of Arrival: December 31
1 g	In-stock	Estimated Time of Arrival: December 31
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Customer Review

Based on 6 publication(s) in Google Scholar

6 Publications Citing Use of MCE MD-224

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von Hippel-Lindau (VHL) Cereblon MDM2 cIAP1

Biological Activity
Purity & Documentation
References
Customer Review

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.

IC₅₀ & Target^[1]

MDM2

1 nM (IC₅₀)

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.

Molecular Weight

889.80

Formula

C₄₈H₄₃Cl₂FN₆O₆

CAS No.

2136247-12-4

Appearance

Solid

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

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)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

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

View the 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, 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
Dilution Calculator

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

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

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In Vivo Dissolution Calculator

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

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Working solution concentration: mg/mL

Purity & Documentation

Purity: 99.60%

Select Batch:

Data Sheet (276 KB) SDS (393 KB)

COA (249 KB) LCMS (94 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]

Complete Stock Solution Preparation Table

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

MD-224 Related Classifications

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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MD-224

Customer Review

MD-224 Related Antibodies

6 Publications Citing Use of MCE MD-224

Featured Recommendations

•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

View All PROTACs Isoform Specific Products:

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References

Customer Review

MD-224 Related Antibodies

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Complete Stock Solution Preparation Table

MD-224 Related Classifications

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