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Purity: ≥98%
MD-224 is a novel, first-in-class and potent PROTAC molecule targeting human murine double minute 2 (MDM2) for degradation, it has the potential to be used as a new class of anticancer agent. It is able to induce rapid degradation of MDM2 protein at a concentration of<1 nM in human leukemia cells, and has an antiproliferative IC50 value of 1.5 nM for inhibiting the growth of RS4;11 cells.
| ln Vitro |
In RS4;11 cells, MD-224 (1-30 nM; 2 hours) efficiently causes MDM2 protein depletion while concurrently causing dose-dependent p53 protein accumulation [1]. In RS4;11 cells, MD-224 (30 nM; 6 hours) is more effective than MI-1061 at causing these p53 target genes to become transcriptionally upregulated, but it has no effect on TP53 itself [1]. At concentrations ≤10 nM, MD-224 (0.001-1 μM; 24 hours) induces strong apoptosis in a dose-dependent manner [1].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: RS4; 11 cells Tested Concentrations: 1 nM; 3 nanomolar; 10 nM; 30 nM Incubation Duration: 2 hrs (hours) Experimental Results: MDM2 protein reduction, p53 protein accumulation. RT-PCR[1] Cell Types: RS4;11 Cell Tested Concentrations: 30 nM Incubation Duration: 6 hrs (hours) Experimental Results: Upregulation of p53 target gene expression. Apoptosis analysis[1] Cell Types: RS4;11 Cell Tested Concentrations: 0.001 μM, 0.003 μM, 0.01 μM, 0.03 μM, 0.1 μM, 0.3 μM, 1 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced in RS4;11 cells Strong apoptosis. |
| 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
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| Molecular Formula |
C₄₈H₄₃CL₂FN₆O₆
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|---|---|
| Molecular Weight |
889.80
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| CAS # |
2136247-12-4
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| Related CAS # |
2136247-12-4;MD-224 HCl;
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| 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
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| Synonyms |
MD224 MD-224 MD 224
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~112.38 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 7.5 mg/mL (8.43 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 75.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 7.5 mg/mL (8.43 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 75.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 2.5 mg/mL (2.81 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: in 5% DMSO + 95% (20% SBE-β-CD in Saline) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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