Nutlin-3a

製品コードS8059 バッチS805905

印刷

化学情報

Chemical Structure Synonyms (-)-Nutlin-3 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C30H30Cl2N4O4
分子量 581.49 CAS No. 675576-98-4
Solubility (25°C)* 体外 DMSO 100 mg/mL (171.97 mM)
Ethanol 100 mg/mL (171.97 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
10.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 200 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Nutlin-3a ((-)-Nutlin-3), the active enantiomer of Nutlin-3, inhibits the p53/MDM2 interaction with IC50 of 90 nM in a cell-free assay. Nutlin-3a induces autophagy and apoptosis in a p53-dependent manner.
in vitro Nutlin-3a displaces p53 from the binding pocket of MDM2 and thereby releases p53 from inhibition and proteasomal degradation, leading to induction of its downstream targets, cell cycle arrest, and apoptosis. Seven days of incubation with 10 μM nutlin-3a led to >90% inhibition of NIH3T3 cells’ growth[1]. Nutlin-3a stabilizes and activates p53, and induces p21 expression in a dose-dependent manner[1]. Nutlin-3a effectively depletes the S-phase compartment to 0.2-2% and increases the G1- and G2/M-phase compartments[1]. Nutlin-3a induces apoptosis in ~60% of SJSA-1 and MHM cells after 40 h, which increased further after 60 h (85% and 65%, respectively) [1].
in vivo Nutlin-3a suppresses xenograft growth in a dose-dependent fashion with the highest dose (200 mg/kg) showing a substantial tumor shrinkage [1]. Nutlin-3 is a selective activator of the p53 pathway in vivo and highly efficacious against SJSA-1 osteosarcoma tumors[1]. Tumors with wild-type p53 and mdm2 gene amplification will respond best to therapy with Nutlin-3a.
特徴 Highly selective MDM2 inhibitor with a much lower effect on MDMX. Most effective on tumors with wild type p53.

プロトコル(参考用のみ)

キナーゼアッセイ Biacore studies
Competition assays are performed on a Biacore S51. A Series S Sensor chip CM5 is derivatized for 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 mm 2). The concentration of MDM2 protein is kept constant at 300 nM. Test compounds are dissolved in DMSO at 10 mM and further diluted to make a concentration series of inhibitor in each MDM2 test sample. The assays are run at 25 °C in running buffer (10 mM Hepes, 0.15 M NaCl, 2% DMSO). MDM2-p53 binding in the presence of inhibitor is calculated as a percentage of binding in the absence of inhibitor and IC50 is calculated using Microsoft Excel
細胞アッセイ 細胞株 OSA, T778, RMS13, U2OS, SaOS-2
濃度 ~5 μM
反応時間 120 h
実験の流れ SRB
動物実験 動物モデル SJSA-1 xenograft
投薬量 50, 100, 200 mg/kg twice daily
投与方法 oral

カスタマーフィードバック

, , J Cell Mol Med, 2017, 21(12):3435-3444

Data from [Data independently produced by , , Oncogene, 2016, 35(42):5552-5564]

Data from [Data independently produced by , , Int J Cancer. 2019, 144(4):777-787]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

SPOCK2 modulates neuropathic pain by interacting with MT1-MMP to regulate astrocytic MMP-2 activation in rats with chronic constriction injury [ J Neuroinflammation, 2024, 21(1):57] PubMed: 38388415
Development of a customizable mouse backbone spectral flow cytometry panel to delineate immune cell populations in normal and tumor tissues [ Front Immunol, 2024, 15:1374943] PubMed: 38605953
Application of prime editing system to introduce TP53 R248Q hotspot mutation in acute lymphoblastic leukemia cell line [ Cancer Sci, 2024, 10.1111/cas.16162] PubMed: 38549229
Integrated drug response prediction models pinpoint repurposed drugs with effectiveness against rhabdomyosarcoma [ PLoS One, 2024, 19(1):e0295629] PubMed: 38277404
A CANCER PERSISTENT DNA REPAIR CIRCUIT DRIVEN BY MDM2, MDM4 (MDMX), AND MUTANT P53 FOR RECRUITMENT OF MDC1 AND 53BP1 TO [ bioRxiv, 2024, 2024.01.20.576487.] PubMed: 38328189
Histone H3 lysine 27 crotonylation mediates gene transcriptional repression in chromatin [ Mol Cell, 2023, 83(13):2206-2221.e11] PubMed: 37311463
The anti-cancer agent APR-246 can activate several programmed cell death processes to kill malignant cells [ Cell Death Differ, 2023, 30(4):1033-1046] PubMed: 36739334
p53 directly downregulates the expression of CDC20 to exert anti-tumor activity in mantle cell lymphoma [ Exp Hematol Oncol, 2023, 12(1):28] PubMed: 36882855
Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53 [ Cell Rep, 2023, 42(12):113478] PubMed: 37991919
SPINK2 Protein Expression Is an Independent Adverse Prognostic Marker in AML and Is Potentially Implicated in the Regulation of Ferroptosis and Immune Response [ Int J Mol Sci, 2023, 24(11)9696] PubMed: 37298647

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。