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）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 10.000mg/ml (17.20mM) 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 of this compound led to >90% inhibition of NIH3T3 cells’ growth[1]. This compound stabilizes and activates p53, and induces p21 expression in a dose-dependent manner[1]. It effectively depletes the S-phase compartment to 0.2-2% and increases the G1- and G2/M-phase compartments[1]. This chemical 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]. This compound 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 this chemical.
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 this compound is calculated as a percentage of binding in the absence of this compound 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

参考

  • https://pubmed.ncbi.nlm.nih.gov/16443686/
  • https://pubmed.ncbi.nlm.nih.gov/21624110/
  • https://pubmed.ncbi.nlm.nih.gov/14704432/

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：

Combined MEK and PARP inhibition enhances radiation response in rectal cancer [ Cell Rep Med, 2025, 6(8):102284] PubMed: 40782795
Chaperone-mediated autophagy directs a dual mechanism to balance premature senescence and senolysis to prevent intervertebral disc degeneration [ Bone Res, 2025, 13(1):62] PubMed: 40506462
WIP1 mutations suppress DNA damage triggered bypass of the mitotic timer [ EMBO J, 2025, 10.1038/s44318-025-00495-0] PubMed: 40551011
Advanced organoid models for targeting Kras-driven lung adenocarcinoma in drug discovery and combination therapy [ J Exp Clin Cancer Res, 2025, 44(1):128] PubMed: 40275403
The Prolonged Half-Life of the p53 Missense Variant R248Q Promotes Accumulation and Heterotetramer Formation with Wildtype p53 to Exert the Dominant-Negative Effect [ Cancer Res, 2025, 10.1158/0008-5472.CAN-24-1136] PubMed: 40163352
Identification of CNOT1-CCR4-NOT as a suppressor of 53BP1-p53-p21 signaling [ Cell Rep, 2025, 44(8):116090] PubMed: 40742806
The puzzling regulation of the interferon signaling system by the p53 tumor suppressor protein [ Cell Mol Life Sci, 2025, 82(1):233] PubMed: 40512405
Reduction of lymphotoxin beta receptor induces cellular senescence via the MDMX-p53 pathway [ Cell Death Discov, 2025, 11(1):416] PubMed: 40883295
CDK11 inhibition induces cytoplasmic p21WAF1 splice variant by p53 stabilisation and SF3B1 inactivation [ Mol Oncol, 2025, 10.1002/1878-0261.70143] PubMed: 41105927
Ferroptosis as a therapeutic vulnerability in MDM2 inhibition in dedifferentiated liposarcoma [ Oncol Lett, 2025, 29(6):269] PubMed: 40247991

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。