548472-68-0
548472-68-0 structure
- Name: Nutlin (3)
- Chemical Name: Nutlin-3
- CAS Number: 548472-68-0
- Molecular Formula: C30H30Cl2N4O4
- Molecular Weight: 581.490
- Catalog: Signaling Pathways Apoptosis MDM-2/p53
- Create Date: 2018-12-09 21:49:21
- Modify Date: 2024-01-02 23:26:45
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Nutlin 3 is a commercial available p53-MDM2 inhibitor, with Ki of 90 nM.
| Name | Nutlin-3 |
|---|---|
| Synonyms |
4-({4,5-bis(4-chlorophenyl)-2-[4-methoxy-2-(propan-2-yloxy)phenyl]-4,5-dihydro-1H-imidazol-1-yl}carbonyl)piperazin-2-one
(+/-)-4-[4,5-BIS(4-CHLOROPHENYL)-2-(2-ISOPROPOXY-4-METHOXY-PHENYL)-4,5-DIHYDRO-IMIDAZOLE-1-CARBONYL]-PIPERAZIN-2-ONE 2-Piperazinone, 4-[[4,5-bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]- 2-Piperazinone,4-[[(4R,5S)-4,5-bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-,rel Piperazinone, 4-[[(4R,5S)-4,5-bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-, rel-;4-[4,5-Bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]piperazin-2-one MFCD07784509 Piperazinone,4-[[(4R,5S)-4,5-bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-,rel 4-{[4,5-Bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazol-1-yl]carbonyl}-2-piperazinone 4-[4,5-Bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]piperazin-2-one NUTLIN-3 Nutlin (3) |
| Description | Nutlin 3 is a commercial available p53-MDM2 inhibitor, with Ki of 90 nM. |
|---|---|
| Related Catalog | |
| Target |
Ki: 90 nM (p53-MDM2)[1] |
| In Vitro | Nutlin 3 is an inhibitor of the MDM2-p53 interaction. In particular, co-treatment of p53-positive HCT116 cells with 1 μM of Inauhzin and 2 μM of Nutlin 3 more significantly activated p53 as measured by its protein level as well as the level of its target p21, PUMA or cleaved PARP as indication of apoptosis[2]. Nutlin 3 is a small-molecule inhibitor that acts to inhibit MDM2 binding to p53 and subsequent p53-dependent DNA damage signaling. As a single agent, Nutlin 3 (2-10 μM) stabilizes p53 and p21WAF levels and is toxic to WTp53-22RV1 cells (IC50, 4.3 μM) but has minimal toxicity toward p53-deficient cells (IC50, >10 μM). Nutlin 3 induces p53 and p21WAF expression in a dose-dependent manner in 22RV1 cells. Short-term cell cycle assays show that, at a dose of 10 μM, Nutlin 3 increasea slightly the G1-phase fraction and decreasea S-phase fraction of all three cell lines[3]. |
| In Vivo | Nutlin 3 can suppress the growth of xenograft tumors derived from human osteosarcoma or leukemia cells, the anti-tumor activity of Nutlin 3 even at the dose of 200 mg/kg per oral administration is marginal in an HCT116-derived xenograft tumor model[2]. Nutlin 3 may be a useful adjunct to improve the therapeutic ratio using precision radiotherapy targeted to hypoxic cells and warrants further study in vivo[3]. |
| Cell Assay | 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[2]. |
| Animal Admin | Mice[2] Five-week-old female SCID mice are used. Mice are subcutaneously inoculated with 3×106 HCT116p53+/+ cells in the right flank and tumor growth is monitored with calipers. After the mean tumor volume reaches 50-100 mm3, animals are administered Inauhzin intraperitoneally (IP), Nutlin 3 orally, or vehicles (4% DMSO for Inauhzin, EtOH: Tween: 5% Glucose=5:5:90 for Nutlin 3). Tumor volume is measured every other day, and inhibition of tumor growth (T/C) is calculated on the last day of treatment. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Molecular Formula | C30H30Cl2N4O4 |
| Molecular Weight | 581.490 |
| Exact Mass | 580.164429 |
| PSA | 83.47000 |
| LogP | 2.77 |
| Index of Refraction | 1.648 |
| Storage condition | -20°C |