NVP-CGM097

Catalog No.S7875 Batch:S787501

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Technical Data

Formula

C38H47ClN4O4
Molecular Weight 659.26 CAS No. 1313363-54-0
Solubility (25°C)* In vitro DMSO 65 mg/mL (98.59 mM)
Ethanol 65 mg/mL (98.59 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 NVP-CGM097 is a highly potent and selective MDM2 inhibitor with Ki value of 1.3 nM for hMDM2 in TR-FRET assay. It binds to the p53 binding-site of the Mdm2 protein, disrupting the interaction between both proteins, leading to an activation of the p53 pathway.
Targets
MDM2 [1]
(Cell-free assay)
1.7 nM
In vitro NVP-CGM097 binding to MDM2 is species dependent. It was shown to be selective for the p53:MDM2 interaction compared to the p53:MDM4 interaction (1176-fold selectivity) and the Ras:Raf interaction (3000-fold selectivity). In addition, NVP-CGM097 showed no significant activity against Bcl-2:Bak, Bcl-2:Bad, Mcl-1:Bak, Mcl-1:NOXA, XIAP:BIR3, and c-IAP:BIR3 protein-protein interactions. NVP-CGM097 was able to significantly redistribute wild-type p53 into the cell nucleus with an IC50 of 0.224 μM, demonstrating its ability to inhibit the p53:MDM2 interaction in living cells. NVP-CGM097 treatment leads to p53 nuclear translocation that results in cell growth inhibition in a p53-dependent manner[1].
In vivo After iv administration, the total blood clearance (CL) of NVP-CGM097 was 5 mL/min/kg for mouse, 7 mL/min/kg for rat, 3 mL/min/kg for dog, and 4 mL/min/kg for monkey. On the basis of the respective hepatic blood flows, NVP-CGM097 showed a consistent low total blood CL in all species (5-10% of hepatic blood flow). The apparent terminal half-life (t1/2) was long in rodents and monkey (6-12 h) but was comparatively longer in dogs (20 h). After oral dosing, the compound was well absorbed with Tmax occurring between 1 and 4.5 h in all species tested. The oral bioavailability (%F) was high in mouse, rat, and dog and moderate in monkey. NVP-CGM097 was able to inhibit the interaction between p53 and MDM2 and reactivate the p53 pathway in vivo in a MDM2-amplified SJSA-1 human tumor model. p21 mRNA levels were found to increase concomitantly with levels of compound 1 in tumor-bearing rats dosed at 30 mg/kg. Daily treatment with NVP-CGM097 dose dependently and significantly inhibited SJSA-1 tumor growth in rats[1].

Protocol (from reference)

Cell Assay:[2]
  • Cell lines

    Bon1 cells, NCI-H727 cells, Got1 cells

  • Concentrations

    0.1 nM-2500 nM

  • Incubation Time

    48 hrs, 96 hrs, 144 hrs or 216 hrs

  • Method

    Cells were seeded in appropriate densities (Bon1 cells: 1500 cells/well, NCI-H727 cells: 2000 cells/well, Got1 cells: 50000 cells/well) into 96-well plates and grown for 24 hrs in complete medium containing serum/antibiotic. The next day, the cells were incubated with various concentrations of NVP-CGM097 (0.1 nM-2500 nM), 5-fluorouracil (100 nM-100 µM), streptozotocin (1 nM-100 µM), temozolomide (1 µM-1 mM), everolimus (10 nM) or octreotide (100 nM-10 µM) in 10 % FBS medium (antibiotic-free). After 48 hrs, 96 hrs, 144 hrs or 216 hrs the metabolic activity was measured with "Cell Titer 96 Aqueous One Solution" cell proliferation assay. The measurement was performed at 492 nm with an ELISA plate reader.

Animal Study:[1]
  • Animal Models

    Sprague-Dawley rat

  • Dosages

    1 mg/kg

  • Administration

    i.v.

Customer Product Validation

Data from [Data independently produced by , , Carcinogenesis, 2013, 34(2):436-445.]

Selleck's NVP-CGM097 has been cited by 6 publications

BCL6 inhibition ameliorates ruxolitinib resistance in CRLF2-rearranged acute lymphoblastic leukemia [ Haematologica, 2022, 10.3324/haematol.2022.280879] PubMed: 36005560
Autophagy augments the self-renewal of lung cancer stem cells by the degradation of ubiquitinated p53 [ Cell Death Dis, 2021, 12(1):98] PubMed: 33468994
Preclinical Evaluation of Drug Combinations Identifies Co-Inhibition of Bcl-2/XL/W and MDM2 as a Potential Therapy in Uveal Melanoma [ Eur J Cancer, 2020, 126:93-103] PubMed: 31927215
Basal Level p53 Suppresses Antiviral Immunity against Foot-and-Mouth Disease Virus [ Viruses, 2019, 11(8)] PubMed: 31394868
Structural Insights into the Pharmacophore of Vinca Domain Inhibitors of Microtubules [Wang Y, et al. Mol Pharmacol, 2016, 89(2):233-42] PubMed: 26660762
Novel pyrimidine-2,4-diamine derivative suppresses the cell viability and spindle assembly checkpoint activity by targeting Aurora kinases. [Salmela AL, et al. Carcinogenesis, 2013, 34(2):436-45] PubMed: 23104179

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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.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.