| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
The primary target is MDM2 (murine double minute 2), an E3 ubiquitin ligase that negatively regulates p53 by binding to its transactivation domain and promoting its degradation. (4R,5S)-nutlin carboxylic acid binds to the p53-binding pocket of MDM2, disrupting the MDM2-p53 interaction. This leads to p53 stabilization and activation of p53 target genes, resulting in cell cycle arrest and apoptosis.
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|---|---|
| ln Vitro |
(4R,5S)-nutlin carboxylic acid is a carboxylic acid derivative of nutlin, an MDM2 antagonist. It binds to MDM2 and disrupts the MDM2-p53 interaction, leading to p53 stabilization. It is used as a research tool to study p53-MDM2 interactions and as a building block for MDM2 inhibitor synthesis. Specific IC50 or Kd values are not widely reported.
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| ln Vivo |
In vivo data for (4R,5S)-nutlin carboxylic acid are limited. As an MDM2 antagonist, it would be expected to show antitumor activity in p53 wild-type xenograft models. However, specific published in vivo efficacy data and dosing regimens are not available in the public domain.
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| Enzyme Assay |
MDM2 binding assays use recombinant MDM2 protein and a fluorescently labeled p53 peptide. (4R,5S)-nutlin carboxylic acid is incubated with MDM2 and the probe in assay buffer. Binding is measured by fluorescence polarization. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Cell-based assays for MDM2 inhibition use p53 wild-type cancer cell lines (e.g., HCT-116, MCF-7). Cells are treated with (4R,5S)-nutlin carboxylic acid (0.1-50 µM) for 24-72 hours. Cell viability is measured by MTT assay. p53 stabilization and target gene expression (e.g., p21, MDM2) are assessed by Western blotting or qRT-PCR.
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| Animal Protocol |
In vivo, (4R,5S)-nutlin carboxylic acid would be tested in mouse xenograft models. A typical protocol would involve intraperitoneal or oral administration (10-100 mg/kg) in mice bearing p53 wild-type tumor xenografts. Tumor volume would be measured. p53 activation in tumor tissue would be assessed by immunohistochemistry for p21.
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| References |
| Molecular Formula |
C32H32CL2N4O6
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|---|---|
| Molecular Weight |
639.5257
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| Exact Mass |
638.169
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| CAS # |
2306390-08-7
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| Related CAS # |
Nutlin carboxylic acid; 2249750-27-2
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| PubChem CID |
138911380
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
5
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| tPSA |
112
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
44
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| Complexity |
1060
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC(C)OC1=C(C=CC(=C1)OC)C2=N[C@@H]([C@@H](N2C(=O)N3CCN(C(=O)C3)CC(=O)O)C4=CC=C(C=C4)Cl)C5=CC=C(C=C5)Cl
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| InChi Key |
CYFZSMNCDNFMOG-IHLOFXLRSA-N
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| InChi Code |
InChI=1S/C32H32Cl2N4O6/c1-19(2)44-26-16-24(43-3)12-13-25(26)31-35-29(20-4-8-22(33)9-5-20)30(21-6-10-23(34)11-7-21)38(31)32(42)37-15-14-36(18-28(40)41)27(39)17-37/h4-13,16,19,29-30H,14-15,17-18H2,1-3H3,(H,40,41)/t29-,30+/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]acetic acid
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 1.5636 mL | 7.8182 mL | 15.6365 mL | |
| 5 mM | 0.3127 mL | 1.5636 mL | 3.1273 mL | |
| 10 mM | 0.1564 mL | 0.7818 mL | 1.5636 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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