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Bortezomib(PS-341 Velcade)
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。
Bortezomib(PS-341 Velcade)图片
CAS NO:179324-69-7
规格:≥98%
包装与价格:
包装价格(元)
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议
1g电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)384.24
FormulaC19H25BN4O4
CAS No.179324-69-7
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 76 mg/mL (197.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)2% DMSO+30% PEG 300+ddH2O: 5 mg/mL
SynonymsPS-341; PS341; NSC 681239; MLN-341; PS 341; LDP 341; LDP-341; LDP341; MLN341; MLN 341. Brand name: VELCADE; NSC681239; NSC-681239
Chemical Name((R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-2-carboxamido)propanamido)butyl)boronic acid
SMILES CodeCC(C)C[C@@H](B(O)O)NC([C@@H](NC(C1=NC=CN=C1)=O)CC2=CC=CC=C2)=O
实验参考方法
In Vitro

In vitro activity: Bortezomib is a boronic acid dipeptide that s a highly selective, reversible inhibitor of the 26S proteasome which primarily functions in the degradation of mis-folded proteins and is essential for the regulation of the cell cycle. Exposure to Bortezomib has been shown to stabilize p21, p27, and p53, as well as the proapoptotic Bid and Bax proteins, caveolin-1, and inhibitor κB-α, which prevents activation of nuclear factor κB-induced cell survival pathways. Bortezomib also promotes the activation of the proapoptotic c-Jun-NH2 terminal kinase, as well as the endoplasmic reticulum stress response. Alteration of the levels of these cellular proteins leads to inhibition of proliferation, migration, and promotion of apoptosis of cancer cells. Bortezomib is shown to penetrate into cells and inhibit proteasome-mediated intracellular proteolysis of long-lived proteins with a concentration that inhibits 50% of the proteolysis of ~0.1 μM. The average growth inhibition of 50% value for Bortezomib across the entire panel of 60 cancer cell lines derived from multiple human tumors from the US National Cancer Institute (NCI) is 7 nM. Treatment of PC-3 cells with Bortezomib (100 nM) for 8 h results in the accumulation of cells in G2-M, with a corresponding decrease in the number of cells in G1. Bortezomib kills PC-3 cells at 24 and 48 hr with IC50 of 100 and 20 nM, respectively. Bortezomib induces nuclear condensation at 16–24 hr after treatment. Bortezomib treatment leads to PARP cleavage in a time-dependent manner with concentrations as low as 100 nM being effective at 24 hr.


Kinase Assay: 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.


Cell Assay: The inhibitory effect of Bortezomib on cell growth is assessed by measuring MTT dye absorbance of the cells. Cells (Human multiple myeloma cells line U266) 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.

In VivoThe anticancer effects of bortezomib as a single agent have been demonstrated in xenograft models of multiple myeloma, adult T-cell leukemia, lung, breast, prostate, pancreatic, head and neck, and colon cancer, and in melanoma. Oral bortezomib 1.0 mg/ kg daily for 18 days causes tumor growth delays, as well as a decrease in the number of metastases in the Lewis lung cancer model. Bortezomib at a single dose of up to 5 mg/kg significantly decreased the surviving fraction of breast tumor cells. Bortezomib 1.0 mg/kg administrated weekly for 4 weeks reduces tumor growth by 60% in murine xenograft models of prostate cancer. 1.0 mg/kg Bortezomib administration for 4 weeks results in a 72% or 84% reduction in pancreatic cancer murine xenografts growth, as well as an increase in tumor cell apoptosis. 1.0 mg/kg Bortezomib treatment results in significant inhibition of human plasmacytoma xenograft growth, increase in tumor cells apoptosis and overall survival, and a decrease in tumor angiogenesis.
Animal modelHuman plasmacytoma xenografts RPMI 8226
Formulation & DosageDissolved in Saline; 1 mg/kg; i.v. injection
ReferencesCancer Res. 1999 Jun 1;59(11):2615-22; Cancer Cell Int. 2005 Jun 1;5(1):18; Cancer Res. 2002 Sep 1;62(17):4996-5000.