There are different enzymes are present in the cell and amongst these enzymes Proteasomes are large enzymes which play function of degrading un-wanted proteins of cells, therefore these enzymes regulate some of the most important pathways including cell cycle and genetic expression. Those compounds which hinder the actions of these proteasomes play important functions in the process of inhibiting the degradation of tumor inhibiting proteins. Because of these properties the proteasome inhibitors such as EGCG (Epigallocatechin-3-gallate) also known as green tea, Salinosporamide-A and Disulfiram have been applied for cancer treatment. Bortezomib is the first approved proteasome inhibitor for clinical trials; this is the most famous inhibitor of this category.
Bortezomib is well recognized and highly selective and specific boronate proteasome inhibitor, in patients of multiple myeloma this was the first proteasome inhibitor to be used during clinical trials. The structure of Bortezomib proteasome inhibitor is based on boric acid and a boron atom plays an important role in its function. For a 1000 mg it costs around $2000 and this is not a fixed price and is variable depending upon its purity and Bortezomib supplier. One can buy Bortezomib from any of the supplier. This compound is soluble in most of organic solvents such as ethanol and DMSO but is poorly soluble in water; 200mg/ml of Bortezomib is made easily. For effective results Bortezomib IC50 is about 10 nM.

Bortezomib proteasome inhibitor plays its inhibitory tasks by a very specific interaction of its boron atom with 26S proteasome representing its active site inactive. In normal cells the binding is usually not rigid and is ineffective while in case of neoplastic cells this inhibition leads to the cell death by apoptosis [1].  In leukemic and lymphoma cells it has been reported that β5 subunit of proteasome having a point mutation G322A can be important as due to this mutation Bortezomib-induced resistance is overcome [2] and this study elaborate the mechanism of action of Bortezomib. In renal cancer, inhibiting the constitutionally the NF-B pathway of cell proliferation and survival was proved as helper in Bortezomib triggered apoptosis [3] and during another research it was shown that the mechanism of Bortezomib also depends on the NF-B down regulation via either p21 gene dependent action in human bladder and prostate cancer cells [4] or by targeting the apoptosis induction by TNF during TRAIL pathway in cases of prostate cancers [5].

During pharmacokinetics studies of Bortezomib it was found as the clearance rate of this compound is high in post-intravenous administration, these properties lead Bortezomib to clinical trials [6]. Bortezomib clinical assessment outcome from patients of lymphoma and a genetic expression profile during clinical trials phase II and III fused its reputation of containing a very good efficacy and safety profile [7] and these were based on the clinical phase II evaluations of relapsed or refractory lymphoma patients [8]. Bortezomib has also been used for prostate cancer during its clinical phase I trials [9]. Although Bortezomib as alone has been used during clinical trials and proved to be very effective in multiple myeloma (MM) [10], many other clinical studies resulted about Bortezomib combination with other anticancer agents such as VEGF (Vascular Endothelial Growth Factor) inhibitors, thalidomide, arsenic trioxide and Lenalidomide [11-12] and it also had synergistic effect on myeloma cells during in-vitro study when used with Thapsigargin [13] and various HDAC (Histone Deacetylases) inhibitors when studied in cancer cells of pancreas [14], in glioma cells Celecoxib [15] though these results are yet be confirmed in clinical trials.

1. Rajkumar, S.V.e.a., Proteasome Inhibition As a Novel Therapeutic Target in Human Cancer. Journal of Clinical Oncology, 2005. 23(3): p. 630-63.
2. Lü, S.e.a., Point Mutation of the Proteasome β5 Subunit Gene Is an Important Mechanism of Bortezomib Resistance in Bortezomib-Selected Variants of Jurkat T Cell Lymphoblastic Lymphoma/Leukemia Line. Journal of Pharmacology and Experimental Therapeutics, 2008. 326(2): p. 423-431.
3. An, J.e.a., VHL expression in renal cell carcinoma sensitizes to bortezomib (PS-341) through an NF-kB-dependent mechanism. Oncogene, 2005. 24: p. 1563-1570.
4. Lashinger, L.M.e.a., Bortezomib Abolishes Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Resistance via a p21-Dependent Mechanism in Human Bladder and Prostate Cancer Cells. Cancer Res, 2005. 65: p. 4902.
5. Nikrad, M.e.a., The proteasome inhibitor Bortezomib sensitizes cells to killing by death receptor ligand TRAIL via BH3-only proteins Bik and Bim. Mol Cancer Ther, 2005. 4: p. 443.
6. Voorhees, P.M.e.a., The proteasome as a target for cancer therapy. Clin Cancer Res, 2003. 9(17): p. 6316-25.
7. Mulligan, G.e.a., Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor Bortezomib. Blood, 2007. 109: p. 3177-3188.
8. Fisher, R.I.e.a., Multicenter Phase II Study of Bortezomib in Patients With Relapsed or Refractory Mantle Cell Lymphoma. Journal of Clinical Oncology, 2006 24(30): p. 4867-4874.
9. Papandreou, C.N.e.a., Phase I Trial of the Proteasome Inhibitor Bortezomib in Patients With Advanced Solid Tumors With Observations in Androgen-Independent Prostate Cancer. Journal of Clinical Oncology, 2004. 22(11): p. 2108-2121.
10. Reeder, C.B.e.a., Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia, 2009. 23: p. 1337-1341.
11. Anargyrou, K.e.a., Novel anti-myeloma agents and angiogenesis. Leuk Lymphoma, 2008. 49(4): p. 677-689.
12. Richardson, P.G.e.a., Novel biological therapies for the treatment of multiple myeloma. Best Pract Res Clin Haematol, 2005. 18(4): p. 619-634.
13. Nawrocki, S.T.e.a., Bortezomib sensitizes pancreatic cancer cells to endoplasmic reticulum stress-mediated apoptosis. Cancer Res, 2005. 65(24): p. 11658-11666.
14. Nawrocki, S.T.e.a., Aggresome disruption: a novel strategy to enhance bortezomib-induced apoptosis in pancreatic cancer cells. Cancer Res, 2006. 66(7): p. 3773-3781.
15. Kardosh, A.e.a., Aggravated endoplasmic reticulum stress as a basis for enhanced glioblastoma cell killing by bortezomib in combination with celecoxib or its non-coxib analogue, 2,5-dimethyl-celecoxib. Cancer Res, 2008. 68(3): p. 843-851.


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Cat.No. Product Name Information
S1013 Bortezomib (PS-341) Bortezomib (PS-341, Velcade, LDP-341, MLM341, NSC 681239) is a potent 20S proteasome inhibitor with Ki of 0.6 nM. It exhibits favorable selectivity towards tumor cells over normal cells. Bortezomib (PS-341) inhibits NF-κB and induces ERK phosphorylation to suppress cathepsin B and inhibit the catalytic process of autophagy in ovarian cancer and other solid tumors.

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