Nutlin-3
Based on 43 publication(s) in Google Scholar
Nutlin-3 is a commercial available p53-MDM2 inhibitor, with Ki of 90 nM.
For research use only. We do not sell to patients.
- Purity: 98.66%
- CAS No.: 548472-68-0
- Formula: C30H30Cl2N4O4
- Molecular Weight:581.49
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
Publications Citing Use of MedChemExpress (MCE) Nutlin-3
More- Cancer Res. 2022 Sep 2;82(17):3032-3044. [Abstract]
- Cancer Res. 2019 Feb 1;79(3):534-545. [Abstract]
- Nat Commun. 2024 Apr 3;15(1):2875. [Abstract]
- Nat Commun. 2024 Mar 18;15(1):2441. [Abstract]
- Cell Death Differ. 2025 Apr 9. [Abstract]
- Cell Discov. 2023 Mar 7;9(1):26. [Abstract]
- Redox Biol. 2026 Mar:90:104043. [Abstract]
- EBioMedicine. 2019 Oct;48:248-263. [Abstract]
- Cancer Lett. 2022 Apr 28:532:215588. [Abstract]
- Adv Healthc Mater. 2025 Apr;14(10):e2404895. [Abstract]
- Cell Death Dis. 2020 Nov 12;11(11):976. [Abstract]
- Dev Cell. 2025 Apr 21;60(8):1182-1198.e8. [Abstract]
- Acta Pharmacol Sin. 2023 Mar;44(3):647-660. [Abstract]
- Mater Sci Eng C Mater Biol Appl. 2020 Mar;108:110403. [Abstract]
- Oncogene. 2026 Apr;45(15):1386-1397. [Abstract]
- Oncogene. 2024 Oct;43(42):3081-3093. [Abstract]
- Cell Rep. 2026 Mar 15;45(3):117084. [Abstract]
- Cell Rep. 2023 Nov 14;42(11):113426. [Abstract]
- Br J Cancer. 2025 Aug 26. [Abstract]
- Anal Chem. 2025 Jul 29;97(29):15687-15697. [Abstract]
- Int J Mol Med. 2021 Jul;48(1):122. [Abstract]
- Int J Mol Med. 2019 Apr;43(4):1758-1768. [Abstract]
- J Ethnopharmacol. 2025 Aug 29:352:120176. [Abstract]
- Int J Oncol. 2022 Mar;60(3):32. [Abstract]
- Eur J Pharmacol. 2025 Oct 10:1007:178233. [Abstract]
- Int Immunopharmacol. 2025 Jun 19:162:115111. [Abstract]
- Eur J Pharmacol. 2025 Jan 24:177289. [Abstract]
- Mol Oncol. 2024 Jan;18(1):6-20. [Abstract]
- Front Mol Biosci. 2021 Aug 19;8:697457. [Abstract]
- Sci Rep. 2025 Aug 19;15(1):30459. [Abstract]
- Sci Rep. 2019 Nov 19;9(1):17050. [Abstract]
- Mol Cell Biochem. 2025 Dec 12. [Abstract]
- Front Oncol. 2025 Jun 24:15:1584811. [Abstract]
- Cell Biol Int. 2025 Jul;49(7):852-864. [Abstract]
- Mol Biol Cell. 2025 Jun 1;36(6):ar64. [Abstract]
- Tissue Cell. 2024 Dec 27:93:102702. [Abstract]
- J Cancer Res Ther. 2025 Dec 1;21(6):1186-1197. [Abstract]
- bioRxiv. 2025 Dec 3.
- Res Sq. 2024 Sep 02.
- bioRxiv. 2024 November 06.
- Res Sq. 2024 Jul 12.
- Research Square Print. 2022 Aug.
- Oncotarget. 2016 Mar 22;7(12):14458-75. [Abstract]
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Cell Imaging/Staining
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Bio/Physico-chemical Assay
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IP
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WB
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Cell Proliferation/Viability Assay
Biological Activity
Ki: 90 nM (p53-MDM2)[1]
Nutlin-3 is an inhibitor of the MDM2-p53 interaction. In particular, co-treatment of p53-positive HCT116 cells with 1 μM of Inauhzin and 2 μM of Nutlin-3 more significantly activated p53 as measured by its protein level as well as the level of its target p21, PUMA or cleaved PARP as indication of apoptosis[2]. Nutlin-3 is a small-molecule inhibitor that acts to inhibit MDM2 binding to p53 and subsequent p53-dependent DNA damage signaling. As a single agent, Nutlin-3 (2-10 μM) stabilizes p53 and p21WAF levels and is toxic to WTp53-22RV1 cells (IC50, 4.3 μM) but has minimal toxicity toward p53-deficient cells (IC50, >10 μM). Nutlin-3 induces p53 and p21WAF expression in a dose-dependent manner in 22RV1 cells. Short-term cell cycle assays show that, at a dose of 10 μM, Nutlin-3 increasea slightly the G1-phase fraction and decreasea S-phase fraction of all three cell lines[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 548472-68-0
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Appearance Solid
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Molecular Weight 581.49
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Formula C30H30Cl2N4O4
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Color White to off-white
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SMILES
O=C1NCCN(C(N2[C@@H](C3=CC=C(Cl)C=C3)[C@@H](C4=CC=C(Cl)C=C4)N=C2C5=CC=C(OC)C=C5OC(C)C)=O)C1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (43)
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Journal Impact Factor
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Most Recent
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Cancer Res
Squalene Epoxidase Metabolic Dependency Is a Targetable Vulnerability in Castration-Resistant Prostate Cancer. [Abstract]2022 Sep 2;82(17):3032-3044. PMID: 35767703
Nutlin-3 purchased from MedChemExpress. Usage Cited in: Cancer Res. 2022 Sep 2;82(17):3032-3044. [Abstract]
Relative luciferase activities of indicated SQLE promoter reporters in C4-2 cells treated with 20 μM LY294002 or 10 μM Nutlin-3 for 12 h.
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Cancer Res
A GYS2/p53 Negative Feedback Loop Restricts Tumor Growth in HBV-Related Hepatocellular Carcinoma. [Abstract]2019 Feb 1;79(3):534-545. PMID: 30584071 -
Nat Commun
ReLo is a simple and rapid colocalization assay to identify and characterize direct protein-protein interactions. [Abstract]2024 Apr 3;15(1):2875. PMID: 38570497
Nutlin-3 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2024 Apr 3;15(1):2875. [Abstract]
Nutlin-3 (5 μM; 24 h). The interaction between p53 1–50 and MDM2 1-118 was inhibited by Nutlin-3 treatment.
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Nat Commun
2024 Mar 18;15(1):2441. PMID: 38499565 -
Cell Death Differ
p53 transcriptionally activates DCP1B to suppress tumor progression and enhance tumor sensitivity to PI3K blockade in non-small cell lung cancer. [Abstract]2025 Apr 9. PMID: 40200093 -
Cell Discov
Reprogramming of palmitic acid induced by dephosphorylation of ACOX1 promotes β-catenin palmitoylation to drive colorectal cancer progression. [Abstract]2023 Mar 7;9(1):26. PMID: 36878899 -
Redox Biol
p53 and fatty acids collaborate to trigger ferroptosis via the FBXO2-FABP5 axis in colorectal cancer. [Abstract]2026 Mar:90:104043. PMID: 41604941 -
EBioMedicine
Zinc-finger protein p52-ZER6 accelerates colorectal cancer cell proliferation and tumour progression through promoting p53 ubiquitination. [Abstract]2019 Oct;48:248-263. PMID: 31521611
Nutlin-3 purchased from MedChemExpress. Usage Cited in: EBioMedicine. 2019 Oct;48:248-263. [Abstract]
Nutlin-3 (5 μM; 24 h). Binding capacity of MDM2 to p53 in HCT116 cells overexpressing p52-ZER6 and treated with Nutlin-3. Cells are treated with MG132 to inhibit proteasomal degradation. Cell lysates are immunoprecipitated against anti-p53 antibody. The presence ofMDM2 is detected by immunoblotting.
Nutlin-3 purchased from MedChemExpress. Usage Cited in: EBioMedicine. 2019 Oct;48:248-263. [Abstract]
Nutlin-3 (5 μM; 24 h). p53 and p21 protein accumulation in HCT116 cells overexpressing p52-ZER6 and treated with Nutlin-3, as examined using western blotting.
Nutlin-3 purchased from MedChemExpress. Usage Cited in: EBioMedicine. 2019 Oct;48:248-263. [Abstract]
Nutlin-3 (5 μM; 24 h). Proliferation of p52-ZER6-overexpressed HCT116 cells treated with nutlin-3, as determined by the EdU incorporation assay. Representative images were shown.
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Cancer Lett
DAB2IP suppresses tumor malignancy by inhibiting GRP75-driven p53 ubiquitination in colon cancer. [Abstract]2022 Apr 28:532:215588. PMID: 35150809 -
Adv Healthc Mater
Engineering Iridium Nanoclusters for Boosting Ferroptotic Cell Death by Regulating GPX4 and p53 Functions. [Abstract]2025 Apr;14(10):e2404895. PMID: 40018815 -
Cell Death Dis
2020 Nov 12;11(11):976. PMID: 33184290 -
Dev Cell
2025 Apr 21;60(8):1182-1198.e8. PMID: 39765233 -
Acta Pharmacol Sin
2023 Mar;44(3):647-660. PMID: 35995868 -
Mater Sci Eng C Mater Biol Appl
A stimuli-responsive combination therapy for recovering p53-inactivation associated drug resistance. [Abstract]2020 Mar;108:110403. PMID: 31923941 -
Oncogene
The NPC1/USP7/p53 axis regulates cholesterol and promotes the proliferation of hepatocellular carcinoma. [Abstract]2026 Apr;45(15):1386-1397. PMID: 41882104 -
Oncogene
2024 Oct;43(42):3081-3093. PMID: 39237765 -
Cell Rep
Loss of p53 exacerbates autoimmunity by reprogramming propionyl-CoA metabolism and histone modifications in Treg cells. [Abstract]2026 Mar 15;45(3):117084. PMID: 41838722 -
Cell Rep
p53-responsive CMBL reprograms glucose metabolism and suppresses cancer development by destabilizing phosphofructokinase PFKP. [Abstract]2023 Nov 14;42(11):113426. PMID: 37967006 -
Br J Cancer
2025 Aug 26. PMID: 40858831 -
Anal Chem
Combining the NanaPPI Toolbox and AI-Driven Virtual Inhibitor Screening for the p53-MDM2 Interaction. [Abstract]2025 Jul 29;97(29):15687-15697. PMID: 40624834 -
Int J Mol Med
Isoquercitrin protects HUVECs against high glucose‑induced apoptosis through regulating p53 proteasomal degradation. [Abstract]2021 Jul;48(1):122. PMID: 33982778 -
Int J Mol Med
SIRT1 inhibits apoptosis in in vivo and in vitro models of spinal cord injury via microRNA-494. [Abstract]2019 Apr;43(4):1758-1768. PMID: 30816451 -
J Ethnopharmacol
Mechanism of action of Pulsatilla chinensis (Bunge) Regel compounds in hepatocellular carcinoma (HCC) treatment: An integrated analysis combining network pharmacology, molecular docking, molecular dynamics simulations and luciferase reporter gene assay. [Abstract]2025 Aug 29:352:120176. PMID: 40543694 -
Int J Oncol
Targeting the TP53/MDM2 axis enhances radiation sensitivity in atypical teratoid rhabdoid tumors. [Abstract]2022 Mar;60(3):32. PMID: 35179215 -
Eur J Pharmacol
Exendin-4 improves mitochondrial integrity against cisplatin-induced cardiac damage: Targeting p53 and NF-κB pathways. [Abstract]2025 Oct 10:1007:178233. PMID: 41075914 -
Int Immunopharmacol
Paeoniflorin mitigates iron overload-induced osteoarthritis by suppressing chondrocyte ferroptosis via the p53/SLC7A11/GPX4 pathway. [Abstract]2025 Jun 19:162:115111. PMID: 40540898 -
Eur J Pharmacol
Hirsutine mitigates ferroptosis in podocytes of diabetic kidney disease by downregulating the p53/GPX4 signaling pathway. [Abstract]2025 Jan 24:177289. PMID: 39864575 -
Mol Oncol
2024 Jan;18(1):6-20. PMID: 37067201 -
Front Mol Biosci
2021 Aug 19;8:697457. PMID: 34490348 -
Sci Rep
2025 Aug 19;15(1):30459. PMID: 40830167 -
Sci Rep
A comprehensive evaluation of pathogenic mutations in primary cutaneous melanomas, including the identification of novel loss-of-function variants. [Abstract]2019 Nov 19;9(1):17050. PMID: 31745173 -
Mol Cell Biochem
APOBEC3B-driven mutations negatively regulated by P53 promote tumor progression and immunosuppressive microenvironment in prostate cancer. [Abstract]2025 Dec 12. PMID: 41385179 -
Front Oncol
p53 enhances elesclomol-Cu-induced cuproptosis in hepatocellular carcinoma via FDXR-mediated FDX1 upregulation. [Abstract]2025 Jun 24:15:1584811. PMID: 40630211 -
Cell Biol Int
2025 Jul;49(7):852-864. PMID: 40329699 -
Mol Biol Cell
Inducible FAK loss but not FAK inhibition in endothelial cells of PYK2-null mice activates p53 tumor suppressor to prevent tumor growth. [Abstract]2025 Jun 1;36(6):ar64. PMID: 40202821 -
Tissue Cell
The role of HM13 expression and its relationship to PI3K/Akt and p53 signaling pathways in colorectal cancer. [Abstract]2024 Dec 27:93:102702. PMID: 39755056 -
J Cancer Res Ther
Inhibition of MDM2 by nutlin-3 decreased pyroptosis but increased apoptosis of lung carcinoma cells under 5-FU chemotherapy. [Abstract]2025 Dec 1;21(6):1186-1197. PMID: 41452010 -
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Oncotarget
Inhibition of WIP1 phosphatase sensitizes breast cancer cells to genotoxic stress and to MDM2 antagonist nutlin-3. [Abstract]2016 Mar 22;7(12):14458-75. PMID: 26883108
Solvent & Solubility
Ethanol : 100 mg/mL (171.97 mM; Need ultrasonic)
DMSO : ≥ 50 mg/mL (85.99 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% EtOH 40% PEG300 5% Tween-80 45% Saline
Solubility: 5 mg/mL (8.60 mM); Clear solution; Need ultrasonic
This protocol yields a clear solution of 5 mg/mL.
Taking 1 mL working solution as an example, add 100 μL EtOH stock solution (50.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% EtOH 90% Corn Oil
Solubility: 5 mg/mL (8.60 mM); Clear solution; Need ultrasonic
This protocol yields a clear solution of 5 mg/mL. If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL EtOH stock solution (50.0 mg/mL) to 900 μL Corn oil, and mix evenly.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (4.30 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (4.30 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
For the following dissolution methods, please prepare the working solution directly:
It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 15% Cremophor EL 85% Saline
Solubility: 15.15 mg/mL (26.05 mM); Clear solution; Need ultrasonic
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
Human non-small-cell lung carcinoma wild type p53-containing H460 and A549, human non-small-cell lung carcinoma p53-null H1299, and human colon cancer HCT116 (p53+/+ and p53-/-) cells are used. Cells (1.5×105) are plated into 6-well plates, and incubated at 37°C overnight. After treatment of Inauhzin and Nutlin 3 at the indicated concentrations for 48 h, cells are harvested, fixed in 70% ice-cold ethanol overnight at -20°C, resuspended in propidium iodide-solution (50 µg/mL PI, 0.1 mg/mL RNase A, 0.05% Tritin X-100 in PBS) for 40 min at 37°C, then analyzed for DNA content using a flow cytometer and proprietary software[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Mice[2]
Five-week-old female SCID mice are used. Mice are subcutaneously inoculated with 3×106 HCT116p53+/+ cells in the right flank and tumor growth is monitored with calipers. After the mean tumor volume reaches 50-100 mm3, animals are administered Inauhzin intraperitoneally (IP), Nutlin 3 orally, or vehicles (4% DMSO for Inauhzin, EtOH: Tween: 5% Glucose=5:5:90 for Nutlin 3). Tumor volume is measured every other day, and inhibition of tumor growth (T/C) is calculated on the last day of treatment.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (292 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
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. [Content Brief]
[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. [Content Brief]
[3]. Supiot S, et al. Nutlin-3 radiosensitizes hypoxic prostate cancer cells independent of p53. Mol Cancer Ther. 2008 Apr;7(4):993-9. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO / Ethanol | 1 mM | 1.7197 mL | 8.5986 mL | 17.1972 mL | 42.9930 mL |
| 5 mM | 0.3439 mL | 1.7197 mL | 3.4394 mL | 8.5986 mL | |
| 10 mM | 0.1720 mL | 0.8599 mL | 1.7197 mL | 4.2993 mL | |
| 15 mM | 0.1146 mL | 0.5732 mL | 1.1465 mL | 2.8662 mL | |
| 20 mM | 0.0860 mL | 0.4299 mL | 0.8599 mL | 2.1497 mL | |
| 25 mM | 0.0688 mL | 0.3439 mL | 0.6879 mL | 1.7197 mL | |
| 30 mM | 0.0573 mL | 0.2866 mL | 0.5732 mL | 1.4331 mL | |
| 40 mM | 0.0430 mL | 0.2150 mL | 0.4299 mL | 1.0748 mL | |
| 50 mM | 0.0344 mL | 0.1720 mL | 0.3439 mL | 0.8599 mL | |
| 60 mM | 0.0287 mL | 0.1433 mL | 0.2866 mL | 0.7166 mL | |
| 80 mM | 0.0215 mL | 0.1075 mL | 0.2150 mL | 0.5374 mL | |
| Ethanol | 100 mM | 0.0172 mL | 0.0860 mL | 0.1720 mL | 0.4299 mL |