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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
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| ln Vitro |
The interaction between MDM2-p53 is inhibited by nutlin-3. Specifically, co-treating p53-positive HCT116 cells with 1 μM Inauhzin and 2 μM Nutlin-3 led to a greater degree of p53 activation for apoptosis (as indicated by p53 protein levels and targets p21, PUMA, or cleaved PARP) [2]. A small molecule inhibitor called nutlin-3 prevents MDM2 from attaching to p53 and the p53-dependent DNA damage signaling that follows. Nutlin-3 (2–10 μM) acts as a single agent to stabilize the levels of p53 and p21WAF. It is toxic to WTp53-22RV1 cells (IC50, 4.3 μM), but only slightly toxic to p53-deficient cells (IC50, >10 μM). Nutlin-3 stimulates the expression of p53 and p21WAF in 22RV1 cells in a dose-dependent manner. In all three cell lines, short-term cell cycle assays revealed that Nutlin-3, at a dose of 10 μM, marginally raised the G1 phase fraction and reduced the S phase fraction [3].
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| ln Vivo |
Nutlin-3 can stop the growth of xenograft tumors made from human osteosarcoma or leukemia cells, however in HCT116-derived xenograft tumor models, Nutlin-3's anti-tumor action is only slightly effective, even at oral dosages of 200 mg/kg. 2]. More in vivo research on nutlin-3 is warranted as it has the potential to be a helpful supplement to enhance the treatment rate of precision radiation directed towards hypoxic cells [3].
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| References |
[1]. Yu Z, et al. Design, synthesis and biological evaluation of sulfamide and triazole benzodiazepines as novel p53-MDM2 inhibitors. Int J Mol Sci. 2014 Sep 5;15(9):15741-53.
[2]. Zhang Y, et al. Inauhzin and Nutlin3 synergistically activate p53 and suppress tumor growth.Cancer Biol Ther. Cancer Biol Ther. 2012 Aug;13(10):915-24. [3]. Supiot S, et al. Nutlin-3 radiosensitizes hypoxic prostate cancer cells independent of p53. Mol Cancer Ther. 2008 Apr;7(4):993-9 |
| Molecular Formula |
C30H30CL2N4O4
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|---|---|
| Molecular Weight |
581.4896
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| CAS # |
548472-68-0
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| Related CAS # |
Nutlin-3a;675576-98-4;Nutlin-3b;675576-97-3;(Rac)-Nutlin-3;890090-75-2
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| SMILES |
ClC1C([H])=C([H])C(=C([H])C=1[H])C1([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([H])C([H])([H])C1([H])[H])=O)=O
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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) |
Ethanol : ~100 mg/mL (~171.97 mM)
DMSO : ≥ 50 mg/mL (~85.99 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (8.60 mM) (saturation unknown) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear EtOH 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: 5 mg/mL (8.60 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix well. View More
Solubility in Formulation 3: ≥ 2.5 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. Solubility in Formulation 4: 2.5 mg/mL (4.30 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 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. Solubility in Formulation 5: 10% DMSO + 90% Corn Oil |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7197 mL | 8.5986 mL | 17.1972 mL | |
| 5 mM | 0.3439 mL | 1.7197 mL | 3.4394 mL | |
| 10 mM | 0.1720 mL | 0.8599 mL | 1.7197 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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