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(Rac)-Nutlin-3

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Chemical Structure| 890090-75-2 同义名 : Nutlin-3;(Rac)-Rebemadlin
CAS号 : 890090-75-2
货号 : A157368
分子式 : C30H30Cl2N4O4
纯度 : 99%+
分子量 : 581.49
MDL号 : MFCD07784509
存储条件：

粉末 Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
靶点

  • E3 Ligase

    MDM2, IC50:180 nM
描述 MDM2 binds the p53 tumor suppressor protein with high affinity and negatively modulates its transcriptional activity and stability. Overexpression of MDM2, found in many human tumors, effectively impairs p53 function. Inhibition of MDM2-p53 interaction can stabilize p53 and may offer a novel strategy for cancer therapy[3]. Nutlin 3a is the active enantiomer of nutlin-3, inhibiting the p53/MDM2 interaction, and IC50 was 90 nM in the cell-free test[4]. In vitro, Nutlin-3a replaces p53 from the binding pocket of the MDM2 protein, thereby releasing p53 from a state of inhibition and proteasome degradation, leading to induction of downstream targets, cell cycle arrest and apoptosis. Incubation for 10 μM Nutlin-3a for 7 days resulted in growth inhibition of NIH3T3 cells of over 90%[5]. Nutlin-3a effectively reduced S-phase cells to 0.2-2% and increased G1- and G2/M- phase cells[5]. After 40 h, Nutlin-3a induced apoptosis in about 60% of SJSA-1 and MHM cells, while at 60 h, the apoptotic cells reached 85% and 65%, respectively[5]. In vivo, Nutlin-3a inhibits xenograft growth in a dose-dependent manner, showing large tumor contractions at the highest dose (200 mg/kg). Nutlin-3a is a selective activator of the p53 pathway in vivo and highly effective against SJSA-1 osteosarcoma. Tumors with wild-type p53 and MDM2 amplification responded best to nutlin-3a therapy[5].
作用机制 Nutlin 3 binds MDM2 in the p53-binding pocket [2].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
115 0.5-10 μM Cell Viability Assay 0-6 d inhibits proliferation in a dose-dependent manner 25067787
115 0.5/1/5 μM Function Assay 48 h leads to increased expression of p53 and some p53 target genes: MDM2, and p21 25067787
115 5 μM Growth Inhibition Assay 48 h induces cell cycle arrest  25067787
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.72mL

0.34mL

0.17mL

8.60mL

1.72mL

0.86mL

17.20mL

3.44mL

1.72mL
参考文献

[1]Thompson T, Tovar C, et al. Phosphorylation of p53 on key serines is dispensable for transcriptional activation and apoptosis. J Biol Chem. 2004 Dec 17;279(51):53015-22.

[2]In vivo activation of the p53 pathway by small-molecule antagonists of MDM2

[3]Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 2004 Feb 6;303(5659):844-8. doi: 10.1126/science.1092472. Epub 2004 Jan 2. PMID: 14704432.

[4]Crane EK, Kwan SY, Izaguirre DI, Tsang YT, Mullany LK, Zu Z, Richards JS, Gershenson DM, Wong KK. 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.

[5]Tovar C, Rosinski J, Filipovic Z, Higgins B, Kolinsky K, Hilton H, Zhao X, Vu BT, Qing W, Packman K, Myklebost O, Heimbrook DC, Vassilev LT. 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.