Bortezomib (PS-341)

Description

Biological Activity

Protocol(Only for Reference)

Clinical Trial Information( data from http://clinicaltrials.gov)

Chemical Information

Preparing Stock Solutions

Customer Reviews (14)

Kinase Assay: [4]

Cell Assay: [5]

Animal Study: [3]

References

貨號 Cat. No.: S1013
規格 Size: 5~200mg
品牌 Brand: Selleckchem

Bortezomib (PS-341)

Catalog No.S1013

14 Reviews 92 Product Citations

Bortezomib (PS-341) is a potent 20S proteasome inhibitor with Ki of 0.6 nM.

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Quantity

10mM/1mLIn DMSO	USD 114	In stock	0 1 2 3 4 5 6 7 8 9 10
5mg	USD 88	In stock	0 1 2 3 4 5 6 7 8 9 10
25mg	USD 340	In stock	0 1 2 3 4 5 6 7 8 9 10
100mg	USD 844	In stock	0 1 2 3 4 5 6 7 8 9 10

Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

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 37â„ƒ 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 lines	Human multiple myeloma cells line U266
Concentrations	~10 μM
Incubation Time	2 days
Method	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.

Animal Models	Human plasmacytoma xenografts RPMI 8226
Dosages	1 mg/kg
Administration	i.v. twice weekly for 4 weeks, then once weekly
Solubility	0.5% methylcellulose/0.2% Tween 80 5 mg/mL

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Phases
NCT02082405	Not yet recruiting	Stage I Multiple Myeloma\|Stage II Multiple Myeloma\|Stage III Multiple Myeloma	Case Comprehensive Cancer Center\|National Cancer Institute (NCI)	Phase 2
NCT02092922	Not yet recruiting	Advanced Multiple Myeloma	Array BioPharma	Phase 2
NCT02093910	Not yet recruiting	Multiple Myeloma	Sun Yat-sen University	Phase 2
NCT02100657	Not yet recruiting	Multiple Myeloma	PharmaMar	Phase 1

Download Bortezomib (PS-341) SDF

Molecular Weight (MW)	384.24
Formula	C19H25BN4O4
CAS No.	179324-69-7

Storage	3 years -20â„ƒPowder
Storage	6 months-80â„ƒin DMSO
Syonnyms	MG-341, PS-341

Solubility (25°C) *	In vitro	DMSO	77 mg/mL (200 mM)
		Water	<1 mg/mL (<1 mM)
		Ethanol	<1 mg/mL (<1 mM)
	In vivo	0.5% methylcellulose/0.2% Tween 80	5 mg/mL
* <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.

Chemical Name

Stock Solution (1ml DMSO)	1mM	10mM	20mM	30mM
Mass(mg)	0.38424	3.8424	7.6848	11.5272

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Description

Bortezomib (PS-341) is a potent 20S proteasome inhibitor with Ki of 0.6 nM.

20S proteasome

0.6 nM (Ki) [1]

In vitro

Bortezomib, a boronic acid dipeptide, is 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 promots 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. [2] 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. [1]

The 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. [2] 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. [3]

Click to enlarge	Rating
	Source	Mireia Vila Gasull University of Porto. 2011;Mireia Vila Gasull .Bortezomib (PS-341) purchased from Selleck
	Method	Western blotting
	Cell Lines	HEK293 cells
	Concentrations	50 μM
	Incubation Time	4 h
	Results	upon proteasome inhibition by Bortezomib an increased amount of around 5–6 fold of biotinylated molecules was detected, both in the absence and presence of US2 and US11.