| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
| Targets |
The primary target of Nutlin carboxylic acid is MDM2 (mouse double minute 2 homolog), an E3 ubiquitin ligase. MDM2 is a negative regulator of the tumor suppressor p53. By binding to MDM2, Nutlin carboxylic acid disrupts the MDM2-p53 interaction. In a PROTAC context, this ligand recruits the MDM2 E3 ligase to a target protein, leading to its ubiquitination and degradation.
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|---|---|
| ln Vitro |
In vitro, Nutlin carboxylic acid functions as an MDM2 ligand. It can inhibit the MDM2-p53 interaction, leading to p53 activation and subsequent apoptosis in cancer cells. When used in PROTACs, it enables the targeted degradation of proteins of interest by recruiting the MDM2 ubiquitin ligase complex. Its carboxylic acid group allows for conjugation to linkers and warheads for PROTAC synthesis.
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| ln Vivo |
In vivo data for Nutlin carboxylic acid are limited, as it is primarily used as a building block for PROTACs. The in vivo efficacy of PROTACs containing this ligand would depend on the target protein and the overall PROTAC design. It holds potential as an anticancer agent and is being investigated in preclinical studies. Further studies are needed to evaluate its activity in animal models.
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| Enzyme Assay |
For MDM2 binding assays, the affinity of Nutlin carboxylic acid for MDM2 can be measured using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). Purified MDM2 protein is immobilized, and varying concentrations of the compound are injected. Binding kinetics and affinity (KD) are calculated. For competition assays, the compound's ability to disrupt MDM2-p53 interaction can be assessed using ELISA or fluorescence polarization.
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| Cell Assay |
For cellular studies, cancer cells are cultured in appropriate medium. Nutlin carboxylic acid is dissolved in DMSO and diluted in culture medium. Cells are treated with the compound or with PROTACs containing this ligand. Cell viability is assessed by MTT assay. p53 activation is measured by Western blot for p53 and its downstream targets (e.g., p21). Protein degradation is assessed by Western blot for the target protein.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice are implanted with cancer cells. PROTACs containing Nutlin carboxylic acid are formulated in vehicle and administered intravenously or intraperitoneally. Tumor growth is monitored. At study termination, tumors are excised and processed for Western blot analysis to assess target protein degradation and p53 pathway activation.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Nutlin carboxylic acid are studied as part of the complete PROTAC molecule. The carboxylic acid group allows for conjugation, and the overall PK depends on the PROTAC's size and linker. The compound's MDM2 binding properties are well-characterized, but specific PK data for the ligand alone are not extensively reported.
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| Toxicity/Toxicokinetics |
Toxicological data for Nutlin carboxylic acid are limited. As a research compound, no acute toxicity, organ-specific toxicity, or mutagenicity data have been reported. As with all research chemicals, appropriate safety precautions should be taken during handling.
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| References |
: Development of Protein Degradation Inducers of Androgen Receptor by Conjugation of Androgen Receptor Ligands and Inhibitor of Apoptosis Protein Ligands. J Med Chem. 2018 Jan 25;61(2):543-575. |
| Additional Infomation |
Nutlin carboxylic acid (CAS 2249750-27-2) is a Nutlin-3-based MDM2 ligand. It has the molecular formula C₃₂H₃₂Cl₂N₄O₆ and a molecular weight of 639.53. It is used in PROTAC design to recruit the MDM2 E3 ligase. It can inhibit the MDM2-p53 interaction and is strictly for research use.
|
| Molecular Formula |
C32H32CL2N4O6
|
|---|---|
| Molecular Weight |
639.5257
|
| Exact Mass |
638.169
|
| CAS # |
2249750-27-2
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| Related CAS # |
(4R,5S)-Nutlin carboxylic acid; 2306390-08-7; (rel)-Nutlin carboxylic acid
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| PubChem CID |
138576186
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| Appearance |
White to yellow solid powder
|
| LogP |
5
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
44
|
| Complexity |
1060
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
ClC1C([H])=C([H])C(=C([H])C=1[H])[C@]1([H])[C@]([H])(C2C([H])=C([H])C(=C([H])C=2[H])Cl)N=C(C2C([H])=C([H])C(=C([H])C=2OC([H])(C([H])([H])[H])C([H])([H])[H])OC([H])([H])[H])N1C(N1C([H])([H])C(N(C([H])([H])C(=O)O[H])C([H])([H])C1([H])[H])=O)=O
|
| InChi Key |
CYFZSMNCDNFMOG-XZWHSSHBSA-N
|
| 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+/m0/s1
|
| Chemical Name |
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]acetic acid
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| HS Tariff Code |
2934.99.9001
|
| 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 : ~50 mg/mL (~78.18 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (4.30 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 27.5 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: ≥ 2.75 mg/mL (4.30 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 27.5 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: ≥ 2.75 mg/mL (4.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| 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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