Bortezomib (PS-341)

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

Price Stock Quantity  
In DMSO USD 91 In stock
USD 70 In stock
USD 270 In stock
USD 670 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

Bortezomib (PS-341) Chemical Structure

Bortezomib (PS-341) Chemical Structure
Molecular Weight: 384.24

Validation & Quality Control

Product Citations(115)

Customer Reviews(14)

Quality Control & MSDS

Related Compound Libraries

Proteasome Inhibitors with Unique Features

  • Pan Proteasome Inhibitor

    Ixazomib (MLN2238) β5 site, IC50=3.4 nM; β1 site, IC50=31 nM; β2 site, IC50=3500 nM.

  • FDA-approved Inhibitor

    Carfilzomib (PR-171) Approved by FDA for multiple myeloma.

  • Newest Proteasome Inhibitor

    Oprozomib (ONX 0912) Orally bioavailable inhibitor for CT-L activity of 20S proteasome β5/LMP7 with IC50 of 36 nM/82 nM.

  • Classic Proteasome Inhibitor

    ONX-0914 (PR-957) Selective immunoproteasome inhibitor with minimal cross-reactivity for the constitutive proteasome.

Product Information

  • Compare Proteasome Inhibitors
    Compare Proteasome Products
  • Research Area
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description Bortezomib (PS-341) is a potent 20S proteasome inhibitor with Ki of 0.6 nM.
Targets 20S proteasome [1]
IC50 0.6 nM(Ki)
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]
In vivo 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]
Features

Protocol(Only for Reference)

Kinase Assay: [4]

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.

Cell Assay: [5]

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 Study: [3]

Animal Models Human plasmacytoma xenografts RPMI 8226
Formulation Saline
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
* 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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Adams J, et al. Cancer Res, 1999, 59(11), 2615-2622.

[2] Boccadoro M, et al. Cancer Cell Int, 2005, 5(1):18.

view more

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2014-09-13)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02220608 Not yet recruiting Multiple Myeloma Washington University School of Medicine October 2014 Phase 1
NCT02237261 Not yet recruiting Multiple Myeloma University Hospital Heidelberg|German Cancer Research Center|Janssen-Cilag International NV|Mundipharma Research GmbH & Co KG|inVentiv Health Clinical October 2014 Phase 2
NCT02201576 Not yet recruiting Chronic Antibody-mediated Transplant Rejection Assistance Publique - Hôpitaux de Paris|CENTAURE Foundation October 2014 Phase 2
NCT02219178 Not yet recruiting Multiple Myeloma ICORG- All Ireland Cooperative Oncology Research Group October 2014 Phase 2
NCT02188537 Not yet recruiting Myeloma Swiss Group for Clinical Cancer Research October 2014 Phase 2

view more

Chemical Information

Download Bortezomib (PS-341) SDF
Molecular Weight (MW) 384.24
Formula

C19H25BN4O4

CAS No. 179324-69-7
Storage 3 years -20℃Powder
6 months-80℃in DMSO
Synonyms LDP-341, MLM341
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.

Research Area

Customer Reviews (14)


Click to enlarge
Rating
Source Development 2011 138, 2903-2908. Bortezomib (PS-341) purchased from Selleck
Method Immunofluorescence
Cell Lines wild-type oocytes, Fmn2-/-oocytes
Concentrations 0.1 μM
Incubation Time 90 min
Results Endogenous Fmn2, localized in the cortex of prophase I oocytes, disappeared at NEBD, reappeared later and was enriched in the cortex opposite the spindle. Fmn2 -/-oocytes lacked cortical Fmn2 staining, suggesting that the staining is specific. Cortical localization was maintained at NEBD in wild-type oocytes treated with the proteasome inhibitor, Bortezomib, indicating that Fmn2 is degraded at NEBD.

Click to enlarge
Rating
Source Carcinogenesis 2010 31, 1948–1955. Bortezomib (PS-341) purchased from Selleck
Method Luciferase assay
Cell Lines LNCaP-AI cells, LNCaP cells
Concentrations 20 μM
Incubation Time 24 h
Results EGF significantly stimulates the promoter activity of sPLA2-IIa gene in both LNCaP and LNCaP-AI cells (shown in LNCaP-AI cells), whereas Bortezomib and other inhibitors tested downregulated the promoter activity both at the basal level (shown in LNCaP cells) and in response to EGF stimulation (shown in LNCaP-AI cells).

Click to enlarge
Rating
Source Carcinogenesis 2010 31, 1948–1955. Bortezomib (PS-341) purchased from Selleck
Method ELISA
Cell Lines LNCaP-AI cells
Concentrations 20 μM
Incubation Time 24 h
Results Bortezomib, Lapatinib, and LY294002 significantly inhibited sPLA2-IIa secretion, whereas Erlotinib, Gefitinib and CI-1033 had a moderate effect in LNCaP-AI cells.

Click to enlarge
Rating
Source J Virol 2010 84, 9439–9451. Bortezomib (PS-341) purchased from Selleck
Method Proteasome activity assay, Standard plaque assay
Cell Lines A549 cells
Concentrations 10-100 nM
Incubation Time 1 h
Results As expected bortezomib treatment resulted in a block of viral replication of the avian influenzavirus strain A/FPV/Bratislava/79 (H7N7; FPV) in a concentration-dependent manner. While concentrations of 10 nM had no antiviral effect, 50 nM led to a significant titer reduction of up to 3 orders of magnitude (Fig.A). The highest concentration used (100 nM) led to a titer reduction of up to 4 orders of magnitude.These results were also confirmed in a virus growth kinetics study in infected cells that received a single dose of 50nM bortezomib. Virus titers were reduced at every time point analyzed (Fig.C).Since bortezomib is a proteasome inhibitor, we investigated whether the antiviral concentrations of bortezomib may have an inhibitory effect on the 26S proteasome in A549 cells. A concentration-dependent inhibition of the proteasome was observed in FPV-infected A549 cells at 24 h p.i. (Fig. B).

Click to enlarge
Rating
Source J Virol 2010 84, 9439–9451. Bortezomib (PS-341) purchased from Selleck
Method Standard plaque assay, Western blot
Cell Lines A549 cells
Concentrations 50 nM
Incubation Time 1-10 h
Results A strong antiviral activity of bortezomib was observed upon addition of the compound up to 2 h p.i. At time points of 4 h p.i. and later, a dramatic decrease in the antiviral efficacy was observed. This indicates that the event in the viral life cycle that is affected by bortezomib occurs within the first 4 h. Since this correlates with the strong onset of viral gene and protein expression, we analyzed whether viral protein accumu-lation is affected by bortezomib. Indeed, we observed a strong reduction in viral matrix protein (M1) and PB1 polymerase synthesis in FPV- and PR8-infected cells at 5 h and 8 h p.i.

Click to enlarge
Rating
Source J Virol 2010 84, 9439–9451. Bortezomib (PS-341) purchased from Selleck
Method Western blot
Cell Lines A549 cells
Concentrations 50 nM
Incubation Time 1/6/24 h
Results After a 6-h treatment with 50 nM bortezomib, activation of JNK was detected as evidenced by phosphorylation of the kinase at Thr183 and Tyr185 (lane 4). This was even enhanced upon a 24-h treatment (lane 6). Downstream substrates of JNK are the AP-1 transcription factors c-Jun and ATF-2, which are activated by JNK-mediated phosphorylation at Ser63 and Thr71, respectively. Consistent with JNK activation, we also found c-Jun and ATF-2 were phosphorylated and activated( lane 6), leading to the conclusion that, besides NF-κB, the JNK/c-Jun/ATF-2 pathway is also activated in A549 upon bortezomib treatment.

Click to enlarge
Rating
Source J Virol 2011 85, 2781–2792. Bortezomib (PS-341) purchased from Selleck
Method Western blot
Cell Lines MA104 cells
Concentrations 0.1-10 μM
Incubation Time 1/7 h
Results Proteasome inhibitors which have different inhibition mechanisms, such as bortezomib and lactacystin, had a strong effect on virus replication in parallel with an increase in p53 accumulation.

Click to enlarge
Rating
Source J Virol 2011 85, 2781–2792. Bortezomib (PS-341) purchased from Selleck
Method Western blot
Cell Lines MA104 cells
Concentrations 10 μM
Incubation Time 5-10 h
Results Further kinetic experiments were performed to better define the time window within the viral replication cycle in which proteasome activity was required. For this, cells were infected for 1 h and treated with MG132 or bortezomib for 4h at different times postinfection (Fig. A). As shown in Fig. B, a more clear arrest on viral protein accumulation was observed when bortezomib or MG132 was added at relatively earlier time points. Indeed, when inhibitors were added at 5 h p.i. or later, the effect was much reduced, suggesting that once the infection was well established with a robust accumulation of viroplasms, the requirement for proteasome activity was less significant.

Click to enlarge
Rating
Source J Virol 2011 85, 2781–2792. Bortezomib (PS-341) purchased from Selleck
Method Immunofluorescence
Cell Lines NSP5-EGFP cells
Concentrations 10 μM
Incubation Time 2-8 h
Results Both MG132 and bortezomib induced a significant arrest on the formation of viroplasms, which appeared in reduced number and with smaller size with respect to those in control cells, particularly when added at time points between 1 h and 5 h p.i.

Click to enlarge
Rating
Source J Virol 2011 85, 2781–2792. Bortezomib (PS-341) purchased from Selleck
Method Quantification of viroplasms
Cell Lines NSP5-EGFP cells, MA104 cells
Concentrations 10 μM
Incubation Time 4 h
Results The number of viroplasms per cell in cells treated for 4 h with MG132 or bortezomib was almost the same as that found in cells fixed at the beginning of each treatment, strongly suggesting that inhibition of proteasome activity affected the assembly of new viroplasms and their growth.

Click to enlarge
Rating
Source J Biol Chem 2010 285, 41074-41086. Bortezomib (PS-341) purchased from Selleck
Method Real Time PCR
Cell Lines HepAD38 cells
Concentrations 2-50 nM
Incubation Time 18 h
Results An inhibitory effect of proteasome inhibition by bortezomib on HBV replication can be observed in cell culture.Therefore, proteasome activation seems to be a valuable strategy of the infected cells to reduce the stress resulting from misfolded proteins.

Click to enlarge
Rating
Source PLoS One 2011 6, e23712. 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.

Click to enlarge
Rating
Source Mireia Vila Gasull University of Porto. 2011;Mireia Vila Gasull . Bortezomib (PS-341) purchased from Selleck
Method PB assay
Cell Lines S2-013
Concentrations
Incubation Time 24 h
Results It is noticed more deleterious effects by free bortezomib than by BTZ CS/GA nanoparticles.

Click to enlarge
Rating
Source 2011 Mireia Vila Gasull University of Porto. Bortezomib (PS-341) purchased from Selleck
Method Western Blotting
Cell Lines KKU-M213 cells
Concentrations 0/20/40 nM
Incubation Time 0-12 h
Results We checked the effects of BTZ on the NF-κB pathway in KKU-M213 (Fig. a, b). BTZ induced IκB phosphorylation in dose- and time-dependent manners (Fig. a). Interestingly, reduced IκB was observed over time until it was barely detectable 12 h after treatment; as a result, nuclear NF-κB (p65) was markedly increased (Fig. b).

Product Citations (115)

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related Proteasome Products

  • PI-1840

    PI-1840 is a reversible and selective chymotrypsin-like (CT-L) inhibitor with IC50 of 27 nM) with little effects on the other two major proteasome proteolytic activities, trypsin-like (T-L) and postglutamyl-peptide-hydrolysis-like (PGPH-L).

  • E-64

    E-64 is an irreversible and selective cysteine protease inhibitor with IC50 of 9 nM for papain.

  • AEBSF HCl

    AEBSF HCl is a broad spectrum, irreversible serine protease inhibitor.

  • MG-132

    MG-132 is an inhibitor of proteasome with IC50 of 100 nM, and also inhibits calpain with IC50 of 1.2 μM.

  • Carfilzomib (PR-171)

    Carfilzomib (PR-171) is an irreversible proteasome inhibitor with IC50 of <5 nM, displayed preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, but little or no effect on the PGPH and T-L activities.

  • ONX-0914 (PR-957)

    ONX-0914 (PR-957) is a potent and selective immunoproteasome inhibitor with minimal cross-reactivity for the constitutive proteasome.

    Features:The first highly selective, small molecule inhibitor of the immunoproteasome. Potential use in cancer and autoimmune diseases (e.g. rheumatoid arthritis, inflammatory bowel disease, and lupus).

  • Ixazomib (MLN2238)

    MLN2238 inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50 and Ki of 3.4 nM and 0.93 nM, respectively, also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites, with IC50 of 31 and 3500 nM.

    Features:A first-in-class proteasome inhibitor that has improved pharmacokinetics (PK), pharmacodynamics(PD), and antitumor activity in preclinical studies.

  • MLN9708

    MLN9708 immediately hydrolyzed to MLN2238, the biologically active form, on exposure to aqueous solutions or plasma. MLN2238 inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50/Ki of 3.4 nM/0.93 nM, less potent to β1 and little activity to β2. Phase 3.

    Features:The 1st oral proteasome inhibitor in early stage clinical trials for Multiple Myeloma.

  • CEP-18770 (Delanzomib)

    CEP-18770 (Delanzomib) is an orally active inhibitor of the chymotrypsin-like activity of proteasome with IC50 of 3.8 nM, with only marginal inhibition of the tryptic and peptidylglutamyl activities of the proteosome. Phase 1/2.

  • Oprozomib (ONX 0912)

    Oprozomib (ONX 0912) is an orally bioavailable inhibitor for CT-L activity of 20S proteasome β5/LMP7 with IC50 of 36 nM/82 nM. Phase 1/2.

Recently Viewed Items

Tags: buy Bortezomib (PS-341) | Bortezomib (PS-341) ic50 | Bortezomib (PS-341) price | Bortezomib (PS-341) cost | Bortezomib (PS-341) solubility dmso | Bortezomib (PS-341) purchase | Bortezomib (PS-341) manufacturer | Bortezomib (PS-341) research buy | Bortezomib (PS-341) order | Bortezomib (PS-341) mouse | Bortezomib (PS-341) chemical structure | Bortezomib (PS-341) mw | Bortezomib (PS-341) molecular weight | Bortezomib (PS-341) datasheet | Bortezomib (PS-341) supplier | Bortezomib (PS-341) in vitro | Bortezomib (PS-341) cell line | Bortezomib (PS-341) concentration | Bortezomib (PS-341) nmr
Contact Us