| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
MDM2 (mouse double minute 2 homolog). MDM2 is an E3 ubiquitin ligase that negatively regulates the p53 tumor suppressor by promoting its ubiquitination and degradation. By degrading MDM2 itself, this compound relieves p53 suppression, activating p53-mediated apoptosis and cell cycle arrest in cancer cells.
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|---|---|
| ln Vitro |
PROTAC MDM2 Degrader-2 induces degradation of MDM2 protein in cells. As a homo-PROTAC, both ends of the molecule bind to MDM2, promoting MDM2 dimerization and subsequent self-ubiquitination and degradation. The compound is expected to show potent MDM2 degradation activity in cancer cell lines expressing wild-type p53. Degradation leads to p53 stabilization and activation of downstream target genes.
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| ln Vivo |
In vivo, PROTAC MDM2 Degrader-2 would be expected to demonstrate antitumor efficacy in xenograft models of p53 wild-type cancers. MDM2 degradation in tumor tissues would lead to p53 activation, apoptosis, and tumor growth inhibition. The compound's PROTAC mechanism provides sustained target suppression compared to conventional MDM2 inhibitors.
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| Enzyme Assay |
MDM2 degradation assays are performed in cell lines (e.g., HCT116, SJSA-1, or RKO) treated with serial dilutions of the compound for 4-24 hours. MDM2 protein levels are quantified by Western blotting or ELISA. p53 and its downstream targets (p21, PUMA, Bax) are also measured to confirm pathway activation. IC₅0 for degradation (DC₅0) is calculated from dose-response curves.
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| Cell Assay |
Cancer cell lines with wild-type p53 are seeded in multi-well plates and treated with PROTAC MDM2 Degrader-2 at various concentrations for 24-72 hours. Cell viability is assessed using MTT, CellTiter-Glo, or colony formation assays. Apoptosis is measured by caspase-3/7 activation or Annexin V staining. Cell cycle analysis is performed by flow cytometry.
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| Animal Protocol |
Mice bearing subcutaneous xenografts of p53 wild-type cancer cells (e.g., HCT116 or SJSA-1) are administered the compound via intraperitoneal or intravenous injection. Tumor growth is monitored, and tumors are harvested for pharmacodynamic analysis of MDM2 degradation, p53 stabilization, and apoptosis markers. Efficacy is determined by tumor growth inhibition and survival.
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| ADME/Pharmacokinetics |
PROTAC MDM2 Degrader-2 has a molecular weight of 1391.22 g/mol and formula C₇0H₇₆Cl4N10O12. As a large PROTAC molecule (>1300 Da), 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. As a PROTAC molecule, potential toxicities may arise from off-target degradation or accumulation of the linker and warhead components. Standard preclinical safety assessment would include cytotoxicity screening, hERG testing, and repeat-dose toxicology in rodents.
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| References | |
| Additional Infomation |
PROTAC MDM2 Degrader-2 is a research compound for cancer studies. It is not clinically approved. The compound is based on patent CN108610333A. As a homo-PROTAC targeting MDM2, it represents a novel strategy for activating the p53 pathway in cancer. The compound is useful for studying MDM2 biology and validating PROTAC technology for cancer therapy.
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| Molecular Formula |
C70H76CL4N10O12
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|---|---|
| Molecular Weight |
1391.22425365448
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| Exact Mass |
1390.436
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| CAS # |
2249944-99-6
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| PubChem CID |
138911384
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
8.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
25
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| Heavy Atom Count |
96
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| Complexity |
2460
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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(NCCOCCOCCNC(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)=O)CC1)=O)=O
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| InChi Key |
WZLSSHVSGKCEKQ-AKOOKZATSA-N
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| InChi Code |
InChI=1S/C70H76Cl4N10O12/c1-43(2)95-57-37-53(91-5)23-25-55(57)67-77-63(45-7-15-49(71)16-8-45)65(47-11-19-51(73)20-12-47)83(67)69(89)81-31-29-79(61(87)41-81)39-59(85)75-27-33-93-35-36-94-34-28-76-60(86)40-80-30-32-82(42-62(80)88)70(90)84-66(48-13-21-52(74)22-14-48)64(46-9-17-50(72)18-10-46)78-68(84)56-26-24-54(92-6)38-58(56)96-44(3)4/h7-26,37-38,43-44,63-66H,27-36,39-42H2,1-6H3,(H,75,85)(H,76,86)/t63-,64-,65+,66+/m1/s1
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| Chemical Name |
2-[4-[(4R,5S)-4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]-2-oxopiperazin-1-yl]-N-[2-[2-[2-[[2-[4-[(4R,5S)-4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]-2-oxopiperazin-1-yl]acetyl]amino]ethoxy]ethoxy]ethyl]acetamide
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ~50 mg/mL (~35.94 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (1.80 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 25.0 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: ≥ 2.5 mg/mL (1.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.7188 mL | 3.5940 mL | 7.1879 mL | |
| 5 mM | 0.1438 mL | 0.7188 mL | 1.4376 mL | |
| 10 mM | 0.0719 mL | 0.3594 mL | 0.7188 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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