Nutlin-3a

Catalog No.S8059 Batch:S805902

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Technical Data

Formula

C30H30Cl2N4O4
Molecular Weight 581.49 CAS No. 675576-98-4
Solubility (25°C)* In vitro DMSO 100 mg/mL (171.97 mM)
Ethanol 100 mg/mL (171.97 mM)
Water Insoluble
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description 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.
Targets
p53-MDM2 interaction [3]
(Cell-free assay)
90 nM
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.
Features Highly selective MDM2 inhibitor with a much lower effect on MDMX. Most effective on tumors with wild type p53.

Protocol (from reference)

Kinase Assay:[3]
  • 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
Cell Assay:[2]
  • Cell lines

    OSA, T778, RMS13, U2OS, SaOS-2

  • Concentrations

    ~5 μM

  • Incubation Time

    120 h

  • Method

    SRB
Animal Study:[1]
  • Animal Models

    SJSA-1 xenograft

  • Dosages

    50, 100, 200 mg/kg twice daily

  • Administration

    oral

Customer Product Validation

, , 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]

Data from [Data independently produced by , , Cancer Lett, 2016, 381(2):370-9]

Selleck's Nutlin-3a has been cited by 92 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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