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
In vivo (Add solvents to the product individually and in order)
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.
* <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.)

Preparing Stock Solutions

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 [ , , Oncogene, 2016, 35(42):5552-5564 ]

Data from [ , , Int J Cancer. 2019, 144(4):777-787 ]

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

Selleck's Nutlin-3a has been cited by 110 publications

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
Ferroptosis as a therapeutic vulnerability in MDM2 inhibition in dedifferentiated liposarcoma [ Oncol Lett, 2025, 29(6):269] PubMed: 40247991
Identification of antibody-drug conjugate payloads which are substrates of ATP-binding cassette drug efflux transporters [ bioRxiv, 2025, 2025.05.22.651305] PubMed: 40501953
Utility of the Base Editing System for Introducing Drug-Resistant Gene Mutations Into Human Leukemia Cellular Models [ Cureus, 2025, 17(4):e81889] PubMed: 40342439
Senolytic compounds reduce epigenetic age of blood samples in vitro [ NPJ Aging, 2025, 11(1):6] PubMed: 39905063
Integrated molecular and functional characterization of the intrinsic apoptotic machinery identifies therapeutic vulnerabilities in glioma [ Nat Commun, 2024, 15(1):10089] PubMed: 39572533
CEP192 localises mitotic Aurora-A activity by priming its interaction with TPX2 [ EMBO J, 2024, 10.1038/s44318-024-00240-z] PubMed: 39327527
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

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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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