| 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 regulates p53 stability. PROTAC MDM2 Degrader-1 targets MDM2 for degradation, relieving p53 from MDM2-mediated inhibition and restoring p53's tumor suppressor functions including cell cycle arrest, apoptosis, and DNA repair.
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|---|---|
| ln Vitro |
PROTAC MDM2 Degrader-1 induces degradation of MDM2 protein in cells. The compound consists of an MDM2 inhibitor, linker, and MDM2 ligand for E3 ligase recruitment. MDM2 degradation leads to p53 stabilization and activation of p53 target genes (p21, PUMA, Bax). The compound is expected to show potent antiproliferative activity in p53 wild-type cancer cells.
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| ln Vivo |
In vivo, PROTAC MDM2 Degrader-1 would be expected to demonstrate antitumor efficacy in xenograft models of p53 wild-type cancers. MDM2 degradation in tumors would activate p53-mediated apoptosis and inhibit tumor growth. The sustained target degradation provided by the PROTAC mechanism may offer advantages over conventional MDM2 inhibitors that only block the MDM2-p53 interaction.
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| Enzyme Assay |
MDM2 degradation assays are performed in p53 wild-type cancer cell lines (e.g., HCT116, SJSA-1). Cells are treated with serial dilutions of the compound for 4-24 hours. MDM2 protein levels are quantified by Western blotting or ELISA. p53 and downstream targets (p21, PUMA) are measured. DC₅0 values are calculated from dose-response curves.
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| Cell Assay |
Cancer cell lines with wild-type p53 are treated with PROTAC MDM2 Degrader-1 at various concentrations for 24-72 hours. Cell viability is assessed using MTT, CellTiter-Glo, or colony formation assays. Apoptosis is measured by caspase activation or Annexin V staining. Cell cycle analysis is performed by flow cytometry to assess G1 arrest or apoptosis.
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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, p53 activation, and apoptosis. Efficacy is determined by tumor growth inhibition and survival extension.
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| ADME/Pharmacokinetics |
PROTAC MDM2 Degrader-1 has a molecular weight of 1463.33 g/mol and formula C₇4H₈4Cl4N10O13. As a large PROTAC molecule (>1400 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. Standard preclinical safety assessment would include cytotoxicity screening, hERG testing, and repeat-dose toxicology in rodents. The compound's large size and linker may influence its toxicity profile compared to small molecule inhibitors.
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| References | |
| Additional Infomation |
PROTAC MDM2 Degrader-1 is a research compound for cancer studies. It is not clinically approved. The compound is based on patent CN108610333A. It serves as a tool for studying MDM2 biology and developing novel cancer therapies through targeted protein degradation. The PROTAC approach offers sustained target suppression and potential activity against resistant mutants.
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| Molecular Formula |
C74H84CL4N10O13
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|---|---|
| Molecular Weight |
1463.32997512817
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| Exact Mass |
1462.494
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| CAS # |
2249944-98-5
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| PubChem CID |
138911383
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| Appearance |
White to off-white solid powder
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| LogP |
9.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
30
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| Heavy Atom Count |
101
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| Complexity |
2550
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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(NCCCOCCOCCOCCCNC(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 |
AQFZQNOXRSZHMG-PQMVWXROSA-N
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| InChi Code |
InChI=1S/C74H84Cl4N10O13/c1-47(2)100-61-41-57(95-5)25-27-59(61)71-81-67(49-9-17-53(75)18-10-49)69(51-13-21-55(77)22-14-51)87(71)73(93)85-33-31-83(65(91)45-85)43-63(89)79-29-7-35-97-37-39-99-40-38-98-36-8-30-80-64(90)44-84-32-34-86(46-66(84)92)74(94)88-70(52-15-23-56(78)24-16-52)68(50-11-19-54(76)20-12-50)82-72(88)60-28-26-58(96-6)42-62(60)101-48(3)4/h9-28,41-42,47-48,67-70H,7-8,29-40,43-46H2,1-6H3,(H,79,89)(H,80,90)/t67-,68-,69+,70+/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-[3-[2-[2-[3-[[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]propoxy]ethoxy]ethoxy]propyl]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 : ~100 mg/mL (~68.34 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.62 mg/mL (0.42 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 6.2 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 | 0.6834 mL | 3.4169 mL | 6.8337 mL | |
| 5 mM | 0.1367 mL | 0.6834 mL | 1.3667 mL | |
| 10 mM | 0.0683 mL | 0.3417 mL | 0.6834 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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