Bosutinib，别名: SKI-606

产品描述

Bosutinib is a synthetic quinolone derivative and dual kinase inhibitor that targets both Abl (IC50: 1 nM) and Src (IC50: 1.2 nM) kinases.

靶点活性

Abl,1nM

c-Src,1.2nM

MAPK,

体外活性

Bosutinib 能够明显抑制Bcr-Abl阳性白血病细胞系KU812（IC50=5 nM）, K562（IC50=20 nM）, 和MEG-01（IC50=20 nM）。Bosutinib作用于Src （IC50=1.2 nM），且有效抑制Src依赖的细胞增殖（IC50=100 nM）。Bosutinib可对乳腺癌细胞运动和入侵有降低（IC50=250 nM），提高细胞间粘附和β-连环蛋白的膜定位。

体内活性

在携带Src-转化纤维移植瘤和HT29移植瘤的裸鼠中，每天用Bosutinib（60 mg/kg）处理，有效抑制肿瘤。在携带Colo205移植瘤的裸鼠中，每天两次用Bosutinib（75 mg/kg）处理，可抑制肿瘤生长，提高剂量后不会有更高效果。小鼠口服Bosutinib100 mg/kg剂量处理可根除大的肿瘤，按150 mg/kg剂量处理可除去肿瘤，且没有毒性。

激酶实验

The Src and Abl kinase assays: The Src kinase activity is measured in an ELISA format. Src (3 units/reaction), reaction buffer (50 mM Tris-HCl pH 7.5, 10 mM MgCl2, 0.1 mM EGTA, 0.5 mM Na3VO4) and cdc2 substrate peptide are added to various concentration of Bosutinib and incubated at 30 °C for 10 minutes. The reaction is started by the addition of ATP to a final concentration of 100 μM, incubated at 30 °C for 1 hour and stopped by addition of EDTA. Instructions from the manufacturer are followed for subsequent steps. The Abl kinase assay is performed in a DELFIA solid phase europium-based detection assay format. Biotinylated peptide (2 μM) is bound to streptavidin-coated microtitration plates for 1.5 hours in 1 mg/mL ovalbumin in PBS. The plates are washed for 1 hour with PBS/0.1% Tween 80, followed by a PBS wash. The kinase reaction is incubated for 1 hour at 30°C. Abl kinase (10 units) is mixed with 50 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 80 μM EGTA, 100 μM ATP, 0.5 mM Na3VO4, 1% DMSO, 1 mM HEPES (pH 7.0), 200 μg/mL ovalbumin and various concentration of Bosutinib. The reaction is stopped with EDTA at a final concentration of 50 mM. The reaction is monitored with Eu-labeled phosphotyrosine antibody and DELFIA enhancement solution.

细胞实验

Cells are exposed to various concentrations of Bosutinib for 72 hours. Anchorage-independent proliferation of Abl-MLV-transformed fibroblasts is measured in 96-well ultra-low binding plates treated with Sigmacote to block residual cell attachment. Cell proliferation is measured with MTS or Cell-Glo. For the determination of cell cycle or cell death, cells are prepared for FACS analysis in the CycleTest Plus DNA reagent kit and analyzed on a fluorescence-activated cell sorter flow cytometer. (Only for Reference)

细胞系： Abl-MLV, Rat 2, KU812, K562, and MEG-01 cells

动物实验

动物模型：Nude femice injected with K562 cells

分子量

530.45

分子式

C26H29Cl2N5O3

CAS

380843-75-4

溶解度

DMSO: 53.1 mg/mL (100 mM)

Ethanol: 13.3 mg/mL (25 mM)

（ < 1 mg/ml refers to the product slightly soluble or insoluble )

储存条件

store at -80°C

备注

For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.