Nutlin-3

SKU: orb1306290

Description

Nutlin-3 is a potent and selective MDM2 antagonist (Ki=90 nM) that stabilizes p53 by blocking its interaction with MDM2. This activation of the p53 pathway confers observed antitumor activity, making it a valuable tool for cancer research in both cellular and animal models.

Research Area

Cell Biology, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 548472-68-0
• MW: 581.51
• Purity: >98%
• Formula: C₃₀H₃₀Cl₂N₄O₄
• SMILES: COc1ccc(C2=NC(C(N2C(=O)N2CCNC(=O)C2)c2ccc(Cl)cc2)c2ccc(Cl)cc2)c(OC(C)C)c1
• Target: Transcription factor
• Solubility: Soluble in DMSO (up to 50 mg/ml), or in Ethanol (up to 50 mg/ml).

Bioactivity

• Target IC50:
  MDM2-p53:0.09 μM
• In Vivo:
  METHODS: To assay antitumor activity in vivo, Nutlin-3 (150 mg/kg, EtOH: Tween: 5% Glucose = 5:5:90; administered orally twice daily for four days and stopped for two days) and Inauhzin (15 mg/kg, intraperitoneally once daily) were administered to SCID mice bearing HCT116 p53+/+ xenografts for 21 days. RESULTS: Each compound alone reduced mean tumor volume by less than 20% after 21 days of treatment. However, when both treatments were combined at the same dose, the final average tumor volume was reduced by 60%. inauhzin and Nutlin-3 activated p53 and inhibited the growth of xenograft tumors in the animals.
• In Vitro:
  METHODS: 22RV1 (p53 WT), DU145 (p53 Mut) and PC-3 (p53 Null) cells were treated with Nutlin-3 (2-10 µM) for 48 h. Apoptosis was detected by Hoechst 33342 staining. RESULTS: Nutlin-3 induced a significant increase in apoptosis in 22RV1 cells, whereas apoptosis was not significantly increased in p53-deficient DU145 or PC-3 cells. Nutlin-3 preferentially increased apoptosis in cells expressing WT p53. METHODS: H460 and HCT116 p53+/+ cells were treated with Nutlin-3 (0-100 µM) and Inauhzin (0-100 µM) for 72 h. Cell viability was measured by WST assay. RESULTS: Inauhzin and Nutlin-3 showed significant synergistic effects in inhibiting the growth of both tumor cell lines, as the CI values were significantly less than 1 in the effective dose range, especially when lower doses of Nutlin-3 were used.
• Cell Research:
  Nutlin-3 (NUT) is dissolved with DMSO (100 mM) and diluted with appropriate media. Human non-small-cell lung carcinoma wild type p53-containing H460 and A549, human non-small-cell lung carcinoma p53-null H1299, and human colon cancer HCT116 (p53+/+ and p53-/-) cells are used. Cells (1.5×105) are plated into 6-well plates, and incubated at 37°C overnight. After treatment of Inauhzin and Nutlin-3 at the indicated concentrations for 48 h, cells are harvested, fixed in 70% ice-cold ethanol overnight at -20°C, resuspended in propidium iodide-solution (50 μg/mL PI, 0.1 mg/mL RNase A, 0.05% Tritin X-100 in PBS) for 40 min at 37°C, then analyzed for DNA content using a flow cytometer and proprietary software.

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

E2 Enzyme, E2 conjugating enzyme, E2Enzyme, E3 Enzyme, E1 activating enzyme, E1 Enzyme, E1/E2/E3 Enzyme, E1Enzyme, E3 ligating enzyme, E3Enzyme, Nutlin 3, Nutlin3, Nutlin-3, inhibit, p53-MDM2, MDM-2/p53, Inhibitor, Ubiquitin ligase, Ubiquitin activating enzyme, Ubiquitin conjugating enzyme

Compound Identifiers

PubChem CID

216345