Nutlin-3a chiral (Synonyms: Nutlin 3a) |
| Catalog No.GC10470 |
Nutlin-3a chiral, an active isomer of Nutlin-3, is a murine double microbody 2 (MDM2) antagonist with IC50 value of 0.09μM .
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Cas No.: 675576-98-4
Sample solution is provided at 25 µL, 10mM.
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Nutlin-3a chiral, an active isomer of Nutlin-3, is a murine double microbody 2 (MDM2) antagonist with IC50 value of 0.09μM . Nutlin-3a chiral inhibits MDM2-p53 interaction and activates wild-type p53, inducing cell cycle arrest and apoptosis[2].
Incubation with 10 μm Nutlin-3a chiral for 7 days resulted in > 90% inhibition of NIH/3T3 cell growth but did not affect MEF proliferation, in which both targets of the drug were eliminated[3].
Nutlin-3a chiral was able to increase the sensitivity to BBR and certain NAX compounds. The effects of Nutlin-3a chiral were usually more substantial in those cells containing an introduced WT TP53 gene[6]. Nutlin-3a chiral binds MDM2 in the TP53-bindingpocket, thereby interfering with MDM2-directed TP53 degradation. This has been shown to cause cell cycle arrest, growth inhibitionand apoptosis in both solid tumors and lymphoid neoplasms.In mantle cell lymphoma(MCL), Nutlin-3a chiral can inhibit cell growth and activate apoptosis in bothwt-TP53(IC50 of 1 to 10μM) and mt-TP53(IC50 of 22.5μM) cells[4]. Nutlin-3a chiral can also effectcell cycle in gastric cancer cell lines. It induces G1 arrest inMKN-45 and SNU-1 cell lines[5].LA-N-5(human neuroblastoma) and SMS-KCNR cells pretreated with Nutlin-3a chiral were significantly more susceptible to DNAM-1-engineered NK cells than NK cells transfected with the empty vector suggesting that the combined use of DNAM-1-chimeric receptor-engineered NK cells and Nutlin-3a chiral may represent a novel therapeutic approach for the treatment of solid tumors, such as NB, carrying dysfunctional p53[7].
In Sjsa-1 tumor-bearing nude mice, Nutlin-3a chiral inhibited xenograft growth in a dose-dependent manner, with the highest dose (200 mg/kg) showing significant tumor shrinkage[3].
References:
[1]: Yang X, Liu J, et,al. miR-18a promotes glioblastoma development by down-regulating ALOXE3-mediated ferroptotic and anti-migration activities. Oncogenesis. 2021 Feb 12;10(2):15. doi: 10.1038/s41389-021-00304-3. PMID: 33579899; PMCID: PMC7881152.
[2]: Crane EK, Kwan SY, et,al. Nutlin-3a: A Potential Therapeutic Opportunity for TP53 Wild-Type Ovarian Carcinomas. PLoS One. 2015 Aug 6;10(8):e0135101. doi: 10.1371/journal.pone.0135101. PMID: 26248031; PMCID: PMC4527847.
[3]: Tovar C, Rosinski J, et,al. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1888-93. doi: 10.1073/pnas.0507493103. Epub 2006 Jan 27. PMID: 16443686; PMCID: PMC1413632.
[4]: Roscoe I, Parker M, et,al. Human Serum Albumin and the p53-Derived Peptide Fusion Protein Promotes Cytotoxicity Irrespective of p53 Status in Cancer Cells. Mol Pharm. 2018 Nov 5;15(11):5046-5057. doi: 10.1021/acs.molpharmaceut.8b00647. Epub 2018 Oct 10. PMID: 30226785.
[5]: Chen R, Zhou J, et,al. A Fusion Protein of the p53 Transaction Domain and the p53-Binding Domain of the Oncoprotein MdmX as an Efficient System for High-Throughput Screening of MdmX Inhibitors. Biochemistry. 2017 Jun 27;56(25):3273-3282. doi: 10.1021/acs.biochem.7b00085. Epub 2017 Jun 14. PMID: 28581721.
[6]: Abrams SL, Akula SM, et,al. Effects of the MDM2 inhibitor Nutlin-3a on sensitivity of pancreatic cancer cells to berberine and modified berberines in the presence and absence of WT-TP53. Adv Biol Regul. 2022 Jan;83:100840. doi: 10.1016/j.jbior.2021.100840. Epub 2021 Nov 23. PMID: 34866036.
[7]: Focaccetti C, Benvenuto M, et,al. DNAM-1-chimeric receptor-engineered NK cells, combined with Nutlin-3a, more effectively fight neuroblastoma cells in vitro: a proof-of-concept study. Front Immunol. 2022 Jul 28;13:886319. doi: 10.3389/fimmu.2022.886319. PMID: 35967339; PMCID: PMC9367496.
| Cell experiment [1]: | |
|
Cell lines |
Mouse NIH/3T3 fibroblasts |
|
Preparation Method |
Exponentially growing mouse NIH/3T3 fibroblasts (wt-TP53) were incubated for 7 days in the presence of Nutlin-3a chiral and stained live by acridine orange. |
|
Reaction Conditions |
10 μM Nutlin-3a chiral for 7 days |
|
Applications |
When tested the activity of Nutlin-3a chiral, on exponentially proliferating mouse NIH/3T3 fibroblasts that express wild-type p53, Seven days of incubation with 10 μM Nutlin-3a chiral led to >90% inhibition of NIH/3T3 cells growth. |
| Animal experiment [2]: | |
|
Animal models |
Sjsa-1 tumor-bearing nude mice |
|
Preparation Method |
Mice were given an oral dose of 200 mg/kg Nutlin-3a chiral twice daily for 2 weeks (LnCaP and 22Rv1) or 3 weeks (MHM) |
|
Dosage form |
200mg/kg Nutlin-3a chiral for 2 or 3 weeks |
|
Applications |
Nutlin-3a chiral inhibited xenograft growth in a dose-dependent manner, with the highest dose (200 mg/kg) showing significant tumor shrinkage |
|
References: [1]. Tovar C, Rosinski J, et,al. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1888-93. doi: 10.1073/pnas.0507493103. Epub 2006 Jan 27. PMID: 16443686; PMCID: PMC1413632. |
|
| Cas No. | 675576-98-4 | SDF | |
| Synonyms | Nutlin 3a | ||
| Chemical Name | 4-[(4S,5R)-4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]piperazin-2-one | ||
| Canonical SMILES | CC(C)OC1=C(C=CC(=C1)OC)C2=NC(C(N2C(=O)N3CCNC(=O)C3)C4=CC=C(C=C4)Cl)C5=CC=C(C=C5)Cl | ||
| Formula | C30H30Cl2N4O4 | M.Wt | 581.49 |
| Solubility | ≥ 29.0745 mg/mL in DMSO, ≥ 104.4 mg/mL in EtOH | Storage | Store at -20°C,protect from light |
| 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 | 0.3439 mL | 1.7197 mL | 3.4394 mL |
| 10 mM | 0.172 mL | 0.8599 mL | 1.7197 mL |
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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