[CAS NO. 890090-75-2]  Nutlin-3

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PRODUCTS SPECIFICATIONS [890090-75-2]

Catalog
SLK-S1061
Brand
Selleck
CAS
890090-75-2

DESCRIPTION [890090-75-2]

Overview

MDL-
Molecular Weight581.5
Molecular FormulaC30H30Cl2N4O4
SMILES-

For research use only.

Storage

3 years,-20°C,powder
1 years,-80°C,in solvent

Shipping

Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

1 mg5 mg10 mg
1 mM1.7197 mL8.5985 mL17.1969 mL
5 mM0.3439 mL1.7197 mL3.4394 mL
10 mM0.1720 mL0.8598 mL1.7197 mL
50 mM0.0344 mL0.1720 mL0.3439 mL

Description

Nutlin-3 is a potent and selective (RING finger-dependent ubiquitin protein ligase for itself and p53) antagonist with of 90 nM in a cell-free assay; stabilizes p73 in p53-deficient cells.

Targets

MDM2 [5]
(Cell-free assay)
180 nM

In vitro

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. 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. 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. 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.

In vivo

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.