Nutlin-3

Nutlin-3は、強力で選択的なMDM-2拮抗剤で、IC50 が 90 nMです。Mdm2は、それ自体とp53のためのRING指依存的なユビキチン・タンパク質リガーゼです。

目録号S1061
5 5 2レビュー 4製品表彰状
価格 在庫  
USD 138 In stock
USD 214 In stock
USD 233 In stock
USD 466 In stock
USD 1222 In stock

Nutlin-3 化学構造
分子量: 581.5

品質と確認

カスタマーレビュー(2)

Quality Control & MSDS

製品情報

  • Compare Mdm2 Inhibitors
    Mdm2阻害剤を比較
  • 研究分野

製品の説明

生物活性

情報 Nutlin-3は、強力で選択的なMDM-2拮抗剤で、IC50 が 90 nMです。Mdm2は、それ自体とp53のためのRING指依存的なユビキチン・タンパク質リガーゼです。
目標 Mdm2
IC50 90 nM [1]
In vitro試験 Nutlin-3 potently inhibits the MDM2-p53 interaction, leading to the activation of the p53 pathway. Nutlin-3 treatment induces the expression of MDM2 and p21, and displays potent antiproliferative activity with IC50 of ~1.5 μM, only in cells with wild-type p53 such as HCT116, RKO and SJSA-1, but not in the mutant p53 cell lines SW480 and MDA-MB-435. In SJSA-1 cells, Nutlin-3 treatment at 10 μM for 48 hours significantly induces caspase-dependent cell apoptosis by ~45%. Although Nutlin-3 also inhibits the growth and viability of human skin (1043SK) and mouse embryo (NIH/3T3) with IC50 of 2.2 μM and 1.3 μM, respectively, cells remain viable 1 week post-treatment even at 10 μM of Nutlin-3, in contrast with the SJSA-1 cells with viability lost at 3 μM of Nutlin-3 treatment. [1] Nutlin-3 does not induce the phosphorylation of p53 on key serine residues and reveals no difference in their sequence-specific DNA binding and ability to transactivate p53 target genes compared with phosphorylated p53 induced by the genotoxic drugs doxorubicin and etoposide, demonstrating that phosphorylation of p53 on key serines is dispensable for transcriptional activation and apoptosis. [2] Although binding less efficiently to MDMX than to MDM2, Nutlin-3 can block the MDMX–p53 interaction and induce the p53 pathway in retinoblastoma cells (Weri1) with IC50 of 0.7 μM. [3] Nutlin-3 at 30 μM also disrupts endogenous p73-HDM2 interaction and enhances the stability and proapoptotic activities of p73, leading to the dose-dependent cell growth inhibition and apoptosis induction in cells without wild-type p53. [4]
In vivo試験 Oral administration of Nutlin-3 at 200 mg/kg twice daily for 3 weeks significantly inhibits the tumor growth of SJAS-1 xenografts by 90%, comparable with the effect of doxorubicin treatment with 81% inhibition of tumor growth. [1]
臨床試験
特集

推薦された実験操作 (公開の文献だけ)

キナーゼアッセイ: [1]

Biacore study Competition assay is performed on a Biacore S51. A Series S Sensor chip CM5 is utilized for the immobilization of a PentaHis antibody for capture of the His-tagged p53. The level of capture is ~200 response units (1 response unit corresponds to 1 pg of protein per mm2). The concentration of MDM2 protein is kept constant at 300 nM. Nutlin-3 is dissolved in DMSO at 10 mM and further diluted to make a concentration series of Nutlin-3 in each MDM2 test sample. The assay is run at 25 °C in running buffer (10 mM Hepes, 0.15 M NaCl, 2% DMSO). MDM2-p53 binding in the presence of Nutlin-3 is calculated as a percentage of binding in the absence of Nutlin-3 and IC50 is calculate

細胞アッセイ: [1]

細胞系 HCT116, RKO, SJSA-1, SW480, and MDA-MB-435
濃度 Dissolved in DMSO, final concentrations ~ 30 μM
処理時間 8, 24, and 48 hours
方法 Cells are exposed to various concentrations of Nutlin-3 for 8, 24 and 48 hours. The transcriptional levels of p21 and MDM2 genes are analyzed by real-time PCR, and protein levels by western blotting. Cell viability is measured by the MTT assay. Cell apoptosis is determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining with flow cytometry and fluorescence microscopy.

動物実験: [1]

動物モデル Athymic female nude mice (Nu/Nu-nuBR) injected subcutaneously with SJSA-1 cells
製剤 Formulated in 2% Klucel, 0.5% Tween 80
投薬量 200 mg/kg
管理 Orally, twice a day
1

参考

化学情報

Download Nutlin-3 SDF
分子量 581.5
化学式

C30H30Cl2N4O4

CAS No. 890090-75-2
保管 2年-20℃
6月-80℃in DMSO
別名
溶解度 (25°C) * In vitro DMSO 100 mg/mL (171 mM)
<1 mg/mL (<1 mM)
エタノール 30 mg/mL (51 mM)
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
化学名 4-(4,5-bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one

研究分野

カスタマーレビュー (2)


Click to enlarge
Rating
Source Cell Death Dis , 2011, 2, e243. Nutlin-3 purchased from Selleck
Method Caspase-Glo 3/7 Assays
Cell Lines UKF-NB-3 cells, UKF-NB-3r cells
Concentrations 10 μM
Incubation Time
Results Investigation of caspase 3/7 activation in response to Nutlin-3 and other cytotoxic drugs revealed that apoptosis induction is reduced and delayed in UKF-NB-3rNutlin10μM cells compared with UKF-NB-3 (Figure 2).

Click to enlarge
Rating
Source Cell Death and Disease (2012) 3, e294. Nutlin-3 purchased from Selleck
Method Western Blot
Cell Lines UKF-NB cells
Concentrations 10 uM
Incubation Time 24 h
Results Only one study has reported an A76T mutation that was found in benign breast tissue. Interestingly, UKF-NB-3’RITA10 uM IV cells were as sensitive to nutlin-3 treatment as parental UKF-NB-3 cells with nutlin-3 treatment resulting in the induction of p53 response gene expression in these cells.

製品表彰状 (4)

技術サポート&よくある質問(FAQ)

顧客がするかもしれない質問に対する答えは、指示を取り扱っている阻害剤で見つかります。話題は、貯蔵液(阻害剤と特別な注意を細胞ベースの分析法と動物のために必要とする問題を保存することは実験します)を準備する方法を含みます。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の問い合わせをするならば、メッセージを残してください。

* 必須

Related Mdm2 阻害剤

  • Nutlin-3a

    Nutlin-3a, the active enantiomer of Nutlin-3, inhibits the p53/MDM2 interaction with IC50 of 90 nM.

  • Nutlin-3b

    Nutlin-3b is a p53/MDM2 antagonist or inhibitor with IC50 value of 13.6 μM, 150-fold less potent (+)-enantiomer of Nutlin-3 as in comparison with opposite (-)-enantiomer Nutlin-3a.

  • YH239-EE

    YH239-EE, the ethyl ester of YH239, is a potent p53-MDM2 antagonist and an apoptosis inducer.

  • GSK2606414

    GSK2606414 is an orally available, potent, and selective PERK inhibitor with IC50 of 0.4 nM, displaying at least 100-fold selectivity over the other EIF2AKs assayed.

  • NSC 207895

    NSC 207895が、リポーター・ベースの薬ふるい分けを通してのMDMX抑制器として発見されます。MDMXは、p53とMDM2(E3リガーゼ)を管理します。

  • ABT-737

    ABT-737は、Bcl-xL、Bcl-2とBcl-wのBH3模倣の阻害剤で、EC50 がそれぞれ78.7 nM、30.3 nM 、197.8 nMになる。

    Features:ABT-737是第一代抗凋亡BCL-2家族蛋白小分子抑制剂。

  • Lenalidomide (CC-5013)

    Lenalidomide (CC-5013) は、13nMのIC50によるTNF-α分泌阻害剤です。

  • ABT-199 (GDC-0199)

    ABT-199 (GDC-0199) is a Bcl-2-selective inhibitor with Kiof < 0.010 nM.

    Features:ABT-263 (Navitoclax)的重组

  • ABT-263 (Navitoclax)

    ABT-263(Navitoclax)は、 Bcl-xLBcl-2Bcl-w の強力な阻害剤で、Kiがそれぞれ ≤ 0.5 nM、≤1 nM 、≤ 1 nMです。

最近見られたアイテム

Tags: Nutlin-3を買う | Nutlin-3供給者 | Nutlin-3を購入する | Nutlin-3費用 | Nutlin-3生産者 | オーダーNutlin-3 | Nutlin-3代理店
お問い合わせ