| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
MDM2 (mouse double minute 2 homolog). As a dimeric or homo-PROTAC, both ends of the molecule bind to MDM2, promoting MDM2 dimerization and self-ubiquitination followed by proteasomal degradation. This mechanism relieves p53 from MDM2-mediated inhibition, activating p53 tumor suppressor functions in cancer cells.
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|---|---|
| ln Vitro |
PROTAC MDM2 Degrader-3 induces degradation of MDM2 protein in cells. As a dimeric PROTAC, it promotes MDM2 self-degradation. MDM2 degradation leads to p53 stabilization and activation of p53 target genes, resulting in cell cycle arrest and apoptosis in p53 wild-type cancer cells. The compound shows potent antiproliferative activity.
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| ln Vivo |
In vivo, PROTAC MDM2 Degrader-3 would be expected to demonstrate antitumor efficacy in xenograft models of p53 wild-type cancers. The dimeric PROTAC mechanism provides sustained MDM2 degradation and p53 activation. Efficacy would be assessed by tumor growth inhibition, pharmacodynamic marker modulation, and survival extension in preclinical models.
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| Enzyme Assay |
MDM2 degradation assays are performed in p53 wild-type cancer cell lines treated with serial dilutions of the compound for 4-24 hours. MDM2 protein levels are quantified by Western blotting. p53 and downstream targets (p21, PUMA, Bax) are measured to confirm pathway activation. DC₅0 values for MDM2 degradation are calculated.
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| Cell Assay |
Cancer cell lines with wild-type p53 are treated with PROTAC MDM2 Degrader-3 at various concentrations for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. Apoptosis is measured by caspase-3/7 activation or Annexin V/PI staining. Cell cycle analysis is performed by flow cytometry to determine cell cycle distribution.
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| Animal Protocol |
Mice bearing subcutaneous xenografts of p53 wild-type cancer cells are administered the compound via intraperitoneal or intravenous injection. Tumor growth is monitored, and tumors are harvested for pharmacodynamic analysis of MDM2 degradation and p53 pathway activation. Efficacy is determined by tumor growth inhibition and survival analysis.
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| ADME/Pharmacokinetics |
PROTAC MDM2 Degrader-3 has a molecular weight of 1437.25 g/mol and formula C₇2H₇₈Cl4N₈O1₅. As a large PROTAC molecule, it may have limited oral bioavailability and is typically administered parenterally. Standard PK parameters would be determined in rodent studies following IV administration.
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| Toxicity/Toxicokinetics |
Toxicology data are not publicly available. Standard preclinical safety assessment would include cytotoxicity screening, hERG testing, and repeat-dose toxicology in rodents. The dimeric nature of this PROTAC may influence its toxicity and pharmacokinetic profile.
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| References | |
| Additional Infomation |
PROTAC MDM2 Degrader-3 is a research compound for cancer studies. It is not clinically approved. As a dimeric MDM2-targeting PROTAC, it represents an innovative approach to activating the p53 pathway. The compound is useful for studying MDM2 biology and developing novel cancer therapeutics based on targeted protein degradation.
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| Molecular Formula |
C72H78CL4N8O15
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|---|---|
| Molecular Weight |
1437.24633550644
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| Exact Mass |
1436.431
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| CAS # |
2249750-23-8
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| PubChem CID |
138911385
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| Appearance |
White to off-white solid powder
|
| LogP |
9.9
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| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
17
|
| Rotatable Bond Count |
30
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| Heavy Atom Count |
99
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| Complexity |
2520
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| Defined Atom Stereocenter Count |
4
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| SMILES |
ClC1C=CC(=CC=1)[C@@H]1[C@H](C2C=CC(=CC=2)Cl)N=C(C2C=CC(=CC=2OC(C)C)OC)N1C(N1CC(N(CC(=O)OCCOCCOCCOCCOC(CN2C(CN(CC2)C(N2C(C3C=CC(=CC=3OC(C)C)OC)=N[C@@H](C3C=CC(=CC=3)Cl)[C@H]2C2C=CC(=CC=2)Cl)=O)=O)=O)CC1)=O)=O
|
| InChi Key |
KECKJSNYFPFODX-PINBWVOXSA-N
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| InChi Code |
InChI=1S/C72H78Cl4N8O15/c1-45(2)98-59-39-55(91-5)23-25-57(59)69-77-65(47-7-15-51(73)16-8-47)67(49-11-19-53(75)20-12-49)83(69)71(89)81-29-27-79(61(85)41-81)43-63(87)96-37-35-94-33-31-93-32-34-95-36-38-97-64(88)44-80-28-30-82(42-62(80)86)72(90)84-68(50-13-21-54(76)22-14-50)66(48-9-17-52(74)18-10-48)78-70(84)58-26-24-56(92-6)40-60(58)99-46(3)4/h7-26,39-40,45-46,65-68H,27-38,41-44H2,1-6H3/t65-,66-,67+,68+/m0/s1
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| Chemical Name |
2-[2-[2-[2-[2-[4-[(4S,5R)-4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]-2-oxopiperazin-1-yl]acetyl]oxyethoxy]ethoxy]ethoxy]ethyl 2-[4-[(4S,5R)-4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]-2-oxopiperazin-1-yl]acetate
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| HS Tariff Code |
2934.99.9001
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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 : ~10 mg/mL (~6.96 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.6958 mL | 3.4789 mL | 6.9577 mL | |
| 5 mM | 0.1392 mL | 0.6958 mL | 1.3915 mL | |
| 10 mM | 0.0696 mL | 0.3479 mL | 0.6958 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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