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R428(BGB-324 R-428)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
R428(BGB-324 R-428)图片
CAS NO:1037624-75-1
规格:≥98%
包装与价格:
包装价格(元)
1mg电议
2mg电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)506.64
FormulaC30H34N8
CAS No.1037624-75-1
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 6 mg/mL (11.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)5% DMSO+corn oil: 1 mg/mL
Chemical Name

(S)-1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N3-(7-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl)-1H-1,2,4-triazole-3,5-diamine

Exact Mass: 506.29064

SMILES CodeNC1=NC(NC2=CC=C3C(CC[C@@H](N4CCCC4)CC3)=C2)=NN1C5=NN=C6C(CCCC7=CC=CC=C76)=C5
SynonymsBGB-324; R428; Bemcentinib; R 428; R-428; BGB324; BGB 324;
实验参考方法
In Vitro

In vitro activity: R428 (also known as BGB324) blocks the catalytic and pro-cancerous activities of Axl. R428 inhibits Axl with low nanomolar activity and blocks Axl-dependent events, including Akt phosphorylation, breast cancer cell invasion, and proinflammatory cytokine production. In a recent study, the Axl inhibitor R428 shows a mean IC50 dose of ~ 2.0μM for the primary CLL B cells after 24 hours of treatment and normal B-, T-, and natural killer (NK) cells show no significant amount of cell death at this dose of R428 (2.5 μM) under similar experimental conditions.


Kinase Assay: R428 (also known as BGB324) is a potent and selective inhibitor of Axl with IC50 of 14 nM,>100-fold selective for Axl versus Abl. The selectivty of R428 for Axl is also greater than Mer and Tyro3 (50-to-100- fold more selective) and InsR, EGFR, HER2, and PDGFRβ (100- fold more selective). A five-point R428 dose titration was performed in radiometric in vitro kinase assays on 133 kinases at the KmATP for each kinase. Axl, Mer, and Tyro3 (Carna Biosciences) assays were also performed using a fluorescence polarization protocol. HER2 activity was determined by Z'-LYTE assay.


Cell Assay: HeLa cells were seeded in starvation medium in 96-well plates. Twenty-four hours later, cells were preincubated for 1 h with diluted R428 before stimulation with preclustered anti-Axl antibody. Cells were fixed, blocked, and stained with anti–phospho-Akt (Ser473) followed by goat anti-rabbit horseradish peroxidase before developing using SuperSignal ELISA Pico chemiluminescent substrate.

In VivoPharmacologic investigations reveal favorable exposure after oral administration such that R428-treated tumors display a dose-dependent reduction in expression of the cytokine granulocyte macrophage colony-stimulating factor and the epithelial-mesenchymal transition transcriptional regulator Snail. In support of an earlier study, R428 inhibits angiogenesis in corneal micropocket and tumor models. R428 administration reduces metastatic burden and extends survival in MDA-MB-231 intracardiac and 4T1 orthotopic (median survival,>80 days compared with 52 days; P < 0.05) mouse models of breast cancer metastasis.
Animal modelMDA-MB-231-luc-D3H2LN Intracardiac Model
Formulation & DosageDissolved in 0.5% hydroxypropylmethylcellulose + 0.1% Tween 80; 125 mg/kg; Oral gavage
ReferencesCancer Res. 2010 Feb 15;70(4):1544-54; Blood. 2011 Feb 10;117(6):1928-37.