印度硼替佐米

产品描述

Bortezomib (PS-341) is a potent 20S proteasome inhibitor (Ki: 0.6 nM, in a cell-free assay).

靶点活性

20S proteasome,0.6nM(Ki)

实验溶液

0.5% methylcellulose+0.2% Tween 80: 5 mg/mL

体外活性

The average growth inhibition of 50% (GI50) value for Bortezomib across the entire NCI cell panel was 7 nM. Bortezomib was shown to penetrate into cells and inhibit proteasome-mediated intracellular proteolysis of long-lived proteins (IC50: 0.1 μM) [1]. Exposure to bortezomib has been shown to stabilize p21, p27, and p53, as well as the proapoptotic Bid and Bax proteins, caveolin-1. Bortezomib also promoted the activation of the proapoptotic c-Jun-NH2 terminal kinase, as well as the endoplasmic reticulum stress response [2]. Bortezomib (0.01-10 μM) treatment caused cell accumulation at the G2-M phase and induced cell apoptotic death in a concentration-dependent manner. The slower mobility of the Bcl-2 band corresponded to the phosphorylation of the Bcl-2 protein and could be seen in the cells exposed to 0.01–0.05 μM Bortezomib for 24 h. Another slower band could be discerned, which corresponded to a superphosphorylated form of Bcl-2, and was detected when cells were exposed to higher concentrations of Bortezomib (0.1–10 μM) for 24 h [3].

体内活性

On 4 consecutive days, Bortezomib (1.0 mg/kg) was administered (in 10 μl) into established PC-3 tumors, and results showed a dramatic decrease in tumor burden. In addition to the large decrease in tumor volume (70%), two of five mice (40%) had no detectable tumors at the end of the study [1]. The mice were injected s.c. with 3 x 10(7) RPMI-8226 myeloma cells. When tumors became measurable, mice were assigned to treatment groups receiving Bortezomib 0.05 mg/kg, 0.1 mg/kg, 0.5 mg/kg, or 1.0 mg/kg twice weekly via the tail vein, or to control groups receiving the vehicle only. Significant inhibition of tumor growth, even with some complete tumor regression, was observed in Bortezomib-treated mice. The median overall survival was also significantly prolonged compared with controls [4].

激酶实验

Kinetic Methods: In a typical kinetic run, 2.00 mL of assay buffer (20 mM HEPES, 0.5 mM EDTA, 0.035% SDS, pH 7.8) and Suc-Leu-Leu-Val-Tyr-AMC in DMSO are added to a 3 mL fluorescence cuvette, and the cuvette is placed in the jacketed cell holder of a fluorescence spectrophotometer. Reaction temperature is maintained at 37℃ by a circulating water bath. After the reaction solution has reached thermal equilibrium (5 minutes), 1 μL−10 μL of the stock enzyme solution is added to the cuvette. Reaction progress is monitored by the increase in fluorescence emission at 440 nm (λex= 380 nm) that accompanies cleavage of AMC from peptide-AMC substrates.

细胞实验

The inhibitory effect of Bortezomib on cell growth is assessed by measuring MTT dye absorbance of the cells. Cells from 48-hour cultures are pulsed with 10 μL of 5 mg/mL MTT to each well for the last 4 hour of 48-hour cultures, followed by 100 μL of isopropanol containing 0.04 N HCl. Absorbance is measured at 570 nm using a spectrophotometer. (Only for Reference)

细胞系： Human multiple myeloma cells line U266

动物实验

动物模型：Human plasmacytoma xenografts RPMI 8226

分子量

384.24

分子式

C19H25BN4O4

CAS

179324-69-7

溶解度

DMSO: 71 mg/mL (184.8 mM)

Ethanol: <1 mg/mL

Water: <1 mg/mL

（ < 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.