GNE-781

製品コードS8665 バッチS866501

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder

化学式

C₂₇H₃₃F₂N₇O₂

分子量

525.59

CAS No.

1936422-33-1

Solubility (25°C)*

体外

DMSO

125 mg/mL (237.82 mM)

Ethanol

100 mg/mL (190.26 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

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.
Clear solution	5%DMSO 1 Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	5.000mg/ml (9.51mM)	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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	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.
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. This compound 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, this compound modulates MYC expression that corresponds with antitumor activity in an AML tumor model.^[1]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	MV-4-11
	濃度	0.002-12.7 μM
	反応時間	4 h
	実験の流れ	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.
動物実験	動物モデル	female 6−9 week-old CD-1 mice
	投薬量	3-30 mg/kg, 1 mg/kg
	投与方法	Oral gavage, IV

参考

https://pubmed.ncbi.nlm.nih.gov/28892380/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。