GNE-781

Catalog No.S8665 Batch:S866501

Technical Data

Formula

C₂₇H₃₃F₂N₇O₂

Molecular Weight

525.59

CAS No.

1936422-33-1

Solubility (25°C)*

In vitro

DMSO

100 mg/mL (190.26 mM)

Ethanol

100 mg/mL (190.26 mM)

Water

Insoluble

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

Clear solution

5%DMSO 1 Corn oil

5.0mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <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

GNE-781 (compound 19) is an orally active, highly potent and selective bromodomain inhibitor of cyclic adenosine monophosphate response element binding protein (CBP) with IC50 of 0.94 nM in TR-FRET assay. GNE-781 also inhibits BRET and BRD4(1) with IC50 of 6.2 nM and 5100 nM, respectively. GNE-781 exhibits antitumor activity.

Targets

CBP ^[1] (in TR-FRET assay)	BRET ^[1] (Cell-free assay)	BRD4(1) ^[1] (Cell-free assay)
0.94 nM	6.2 nM	5100 nM

In vitro

In vitro studies show that GNE-781 reduces FOXP3 (forkhead box P3) transcript levels with a less optimal chemical probe, suggesting that inhibition of the CBP bromodomain may provide a novel small molecule therapeutic approach for cancer immunotherapy. GNE-781 decreases the generation of iTregs in vitro without affecting cell viability.^[1]

In vivo

GNE-781, a highly potent and selective CBP inhibitor that is efficacious in a MOLM-16 AML xenograft model. In vivo, GNE-781 modulates MYC expression that corresponds with antitumor activity in an AML tumor model.^[1]

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines MV-4-11 Concentrations 0.002-12.7 μM Incubation Time 4 h Method To determine the inhibition of MYC expression, MV-4-11 cells (ATCC) sre plated at 10000 cells per well in 96-well plates in RPMI1640 media supplemented with 10% fetal bovine serum and 2 mM L-glutamine. GNE-781 diluted in DMSO are transferred to the cell plates, keeping final DMSO concentration consistent at 0.1%, and incubated for 4 h at 37 °C. Lysis and analysis for MYC expression are carried out using QuantiGene 2.0 reagents and following the vendor’s instructions. Luminescence is read using an EnVision plate reader and EC50s are generated in XLFit using a fourparameter nonlinear regression fit.
Animal Study:^{^[1]}	Animal Models female 6−9 week-old CD-1 mice Dosages 3-30 mg/kg, 1 mg/kg Administration Oral gavage, IV

Cell Assay:^{^[1]}

Cell lines
MV-4-11
Concentrations
0.002-12.7 μM
Incubation Time
4 h
Method
To determine the inhibition of MYC expression, MV-4-11 cells (ATCC) sre plated at 10000 cells per well in 96-well plates in RPMI1640 media supplemented with 10% fetal bovine serum and 2 mM L-glutamine. GNE-781 diluted in DMSO are transferred to the cell plates, keeping final DMSO concentration consistent at 0.1%, and incubated for 4 h at 37 °C. Lysis and analysis for MYC expression are carried out using QuantiGene 2.0 reagents and following the vendor’s instructions. Luminescence is read using an EnVision plate reader and EC50s are generated in XLFit using a fourparameter nonlinear regression fit.

Animal Study:^{^[1]}

Animal Models
female 6−9 week-old CD-1 mice
Dosages
3-30 mg/kg, 1 mg/kg
Administration
Oral gavage, IV

References

[1] F Anthony Romero, et al. J Med Chem. 2017 Nov 22;60(22):9162-9183.

Selleck's GNE-781 has been cited by 2 publications

Multimodal Therapy Approaches for NUT Carcinoma by Dual Combination of Oncolytic Virus Talimogene Laherparepvec with Small Molecule Inhibitors [ Viruses, 2024, 16(5)775]	PubMed: 38793657
Characterization of molecular mechanisms driving Merkel cell polyomavirus oncogene transcription and tumorigenic potential [ PLoS Pathog, 2023, 19(8):e1011598]	PubMed: 37647312

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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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