(±)-Nutlin-3 (Synonyms: Nutlin 3b) |
| Catalog No.GC14154 |
(±)-Nutlin-3 is a potent and selective MDM2 antagonist with IC50 value of 0.09μM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 548472-68-0
Sample solution is provided at 25 µL, 10mM.
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(±)-Nutlin-3 is a potent and selective MDM2 antagonist with IC50 value of 0.09μM[1]. Mouse double minute 2 homolog (MDM2) is an important negative regulator of the tumor suppressor p53, and disrupting the p53-MDM2 interaction activates p53 to inhibit tumor growth[2]. (±)-Nutlin-3 is usually used in the study of tumorigenesis mechanisms and p53 function[3].
In vitro, (±)-Nutlin-3 (10μM; 24h) reduced clonogenic survival of 22RV1 prostate cancer cells, stabilized p53 and p21 proteins, induced G1 arrest and slightly increased apoptosis[4]. (±)-Nutlin-3 (10μM; 48h) markedly induced apoptosis in 29/30 primary B-CLL samples (Annexin-V positivity, loss of ΔΨm, Caspase-3 activation and PARP cleavage), while up-regulating p53, p21, TRAIL-R2 and PIG3 expression, and showed minimal toxicity toward normal CD19⁺ B cells and CD34⁺ hematopoietic progenitors[5].
In vivo, (±)-Nutlin-3 (150mg/kg; p.o.; twice daily for 21 days) combined with Inauhzin (15mg/kg; i.p.; once daily for 21 days) significantly reduced HCT116p53⁺/⁺ xenograft tumor volume in nude mice by 60%, elevated intratumoral p53 and PUMA protein levels, increased TUNEL-positive apoptotic cells and decreased BrdU-labeled proliferating cells[6]. (±)-Nutlin-3 (200mg/kg; p.o.; twice daily for 3 weeks) markedly suppressed primary tumor growth in UKF-NB-3rDOX20 (WT p53) multidrug-resistant neuroblastoma xenografts in nude mice, decreased hepatic and pulmonary MYCN DNA and mRNA levels, reduced metastatic foci and enhanced intratumoral Caspase-3 activity, whereas no effect was observed in p53-mutant UKF-NB-3rVCR10 xenografts[7].
References:
[1] Yu Z, Zhuang C, Wu Y, et al. Design, synthesis and biological evaluation of sulfamide and triazole benzodiazepines as novel p53-MDM2 inhibitors. Int J Mol Sci. 2014;15(9):15741-15753.
[2] Shinohara T, Uesugi M. In-vivo activation of the p53 pathway by small-molecule antagonists of MDM2.Tanpakushitsu Kakusan Koso. 2007;52(13 Suppl):1816-1817.
[3] Secchiero P, Bosco R, Celeghini C, Zauli G. Recent advances in the therapeutic perspectives of Nutlin-3. Curr Pharm Des. 2011;17(6):569-577.
[4] Supiot S, Hill RP, Bristow RG. Nutlin-3 radiosensitizes hypoxic prostate cancer cells independent of p53. Mol Cancer Ther. 2008;7(4):993-999.
[5] Secchiero P, Barbarotto E, Tiribelli M, et al. Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL). Blood. 2006;107(10):4122-4129.
[6] Zhang Y, Zhang Q, Zeng SX, Zhang Y, Mayo LD, Lu H. Inauhzin and Nutlin3 synergistically activate p53 and suppress tumor growth. Cancer Biol Ther. 2012;13(10):915-924.
[7] Van Maerken T, Ferdinande L, Taildeman J, et al. Antitumor activity of the selective MDM2 antagonist nutlin-3 against chemoresistant neuroblastoma with wild-type p53. J Natl Cancer Inst. 2009;101(22):1562-1574.
| Cell experiment [1]: | |
Cell lines | Human malignant prostate cancer 22RV1 cells |
Preparation Method | Human malignant prostate cancer 22RV1 cells were grown in RPMI 1640 supplemented with 10% FCS and 1% L-glutamine. Cells were counted and plated at different densities 15h before (±)-Nutlin-3 exposure. Then cells were treated with 10μM (±)-Nutlin-3 for 24h. Cells were irradiated at room temperature using a 137Cs g-ray irradiator at a dose rate of 0.9 Gy/min. Following incubation, drug was removed and fresh medium was added. Colonies were stained and counted under a microscope, with 50 cells as the minimum number to define a surviving colony. The best-fit survival curve was generated according to a linear-quadratic survival model and the mean inactivation dose (area under survival curve) was calculated. |
Reaction Conditions | 10μM; 24h |
Applications | (±)-Nutlin-3 reduced clonogenic survival of 22RV1 prostate cancer cells. |
| Animal experiment [2]: | |
Animal models | female SCID mice |
Preparation Method | Five-week-old female SCID mice were subcutaneously inoculated with 3×106 HCT116p53+/+ cells in the right flank and tumor growth was monitored with calipers. After the mean tumor volume reached 50–100mm3, animals were administered Inauhzin (15mg/kg; i.p.; once daily for 21 days), (±)-Nutlin-3 (150mg/kg; p.o.; twice daily for 21 days), or vehicles (4% DMSO for Inauhzin, EtOH:Tween:5% glucose = 5:5:90 for (±)-Nutlin-3). Tumor volume was measured every other day, and inhibition of tumor growth (T/C) was calculated on the last day of treatment. To determine p53 induction in vivo, tumors were harvested and homogenized in RIPA buffer with a protease inhibitor mixture. Tumor homogenates were analyzed by western blot. |
Dosage form | 150mg/kg; p.o.; twice daily for 21 days |
Applications | (±)-Nutlin-3 combined with Inauhzin significantly reduced HCT116p53⁺/⁺ xenograft tumor volume in nude mice by 60%, elevated intratumoral p53. |
References: | |
| Cas No. | 548472-68-0 | SDF | |
| Synonyms | Nutlin 3b | ||
| Chemical Name | 4-(4,5-bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one | ||
| Canonical SMILES | ClC1=CC=C(C=C1)C2N(C(N(C3)CCNC3=O)=O)C(C(C=CC(OC)=C4)=C4OC(C)C)=NC2C(C=C5)=CC=C5Cl | ||
| Formula | C30H30Cl2N4O4 | M.Wt | 581.49 |
| Solubility | DMSO : ≥ 50 mg/mL (85.99 mM) Water : < 0.1 mg/mL (insoluble) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.7197 mL | 8.5986 mL | 17.1972 mL |
| 5 mM | 343.9 μL | 1.7197 mL | 3.4394 mL |
| 10 mM | 172 μL | 859.9 μL | 1.7197 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >99.00%
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Average Rating: 5 (Based on Reviews and 32 reference(s) in Google Scholar.)
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