GNE-781

Catalog No.S8665

For research use only.

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.

GNE-781 Chemical Structure

CAS No. 1936422-33-1

Purity & Quality Control

Choose Selective Epigenetic Reader Domain Inhibitors

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 Research:

[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 Research:

[1]

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

Solubility (25°C)

In vitro

DMSO 100 mg/mL
(190.26 mM)
Water Insoluble
Ethanol '''100 mg/mL

Chemical Information

Molecular Weight 525.59
Formula

C27H33F2N7O2

CAS No. 1936422-33-1
Storage 3 years -20°C powder
2 years -80°C in solvent

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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