Bortezomib

SKU: orb1305542

Description

Bortezomib is a potent, selective, and reversible inhibitor of the 20S proteasome (Ki=0.6 nM). Its antitumor activity is linked to NF-κB inhibition, leading to cell cycle arrest and apoptosis, making it a key tool for cancer research in both cellular and animal models.

Research Area

Cardiovascular Research, Protein Biochemistry

Key Properties

• CAS Number: 179324-69-7
• MW: 384.2
• Purity: >98%
• Formula: C₁₉H₂₅BN₄O₄
• SMILES: CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)c1cnccn1)B(O)O
• Target: Proteasome
• Solubility: Soluble in DMSO (up to 50 mg/ml) or in Ethanol (up to 35 mg/ml).

Bioactivity

• Target IC50:
  A549 cells:13.9 nM|20S proteasome:0.6 nM (cell free)|A431 cells:28.2 nM|5TGM1 cells:6.78 nM|A2780 cells:28.9 nM
• In Vivo:
  METHODS: To detect anti-tumor activity in vivo, Bortezomib (0.3 mg/kg) was administered intraperitoneally to NOD/SCID mice bearing primary exudative lymphoma (PEL) UM-PEL-1 once daily for three weeks. RESULTS: Bortezomib induced remission of PEL and prolonged overall survival of mice with lymphoma exudates. bortezomib downregulated cell cycle progression, DNA replication, and Myc target genes. METHODS: To investigate the effect of Bortezomib on renal fibrosis, Bortezomib (0.5 mg/kg) was intraperitoneally injected into an aristolochic acid I (AA)-induced fibrotic C57BL/6J mouse model twice a week for ten weeks. RESULTS: Bortezomib treatment significantly attenuated AA-induced renal dysfunction and proteinuria, reduced the expression of renal fibrosis-associated proteins and markers of renal injury, such as αSMA, Kim1, and Ngal, and prevented renal fibrosis at histopathologic level.
• In Vitro:
  METHODS: Human tongue squamous carcinoma cells SCC-15 and CAL-27, human pharyngeal squamous carcinoma cells FaDu, and human salivary gland carcinoma cells A-253 and SALTO-5 were treated with Bortezomib (6.25-100 nM) for 24-72 h. The growth inhibition of these cells was detected by SRB. RESULTS: The effects of Bortezomib on the proliferation of the five tumor cells were dose- and time-dependent, and SCC-15 was the most sensitive cell to the effects of Bortezomib. SCC-15 was the most sensitive cell to the effect of Bortezomib. METHODS: Human small cell lung cancer cells NCI-H69 and NCI-H2171 were treated with Bortezomib (0.05 μM; 0.5 μM) for 48 h. Cell cycle and apoptosis were detected by Flow Cytometry. RESULTS: Bortezomib induced cell cycle arrest in the G2-M transition state, increased the number of G2-phase cells and decreased the number of S-phase cells, and induced apoptosis in tumor cells. METHODS: H460, a large cell lung cancer cell, was incubated with Bortezomib (0.01-10 μM) for 3-48 h, and the expression levels of target proteins were detected by Western Blot. RESULTS: Bortezomib treatment resulted in concentration-dependent phosphorylation of Bcl-2 protein. Starting at 12 h, a recognizable Bcl-2 cleavage product was observed, and Bcl-2 phosphorylation preceded Bcl-2 cleavage for at least 9 h.
• Cell Research:
  PC-3 cells were treated with different doses of PS-341 for different periods of time. The cells were washed with PBS, harvested, and fixed in suspension with 3.7% formaldehyde in the neutral buffer for 10 min at room temperature. The cells were centrifuged, and the cell pellet was resuspended in 0.5 ml of 80% ethanol. The cell suspension (25–50 μl) was then placed onto a microscope slide precoated with poly-l-lysine and air-dried. The slides were washed four times with 0.1% Triton X-100 in PBS. The slide was incubated with the DNA stain Hoechst 33342 (Molecular Probes; 1.0 μg/ml in PBS with 0.1% Triton-X-100) for 1.0 min. The slides were rinsed in PBS and mounted with 70% glycerol containing 25 mg/ml 1,4-diazabicyclo[2.2.2]octane. Nuclear staining was visualized using a fluorescent microscope .
• Animal Research:
  Mice were inoculated s.c. into the right flank with 3 × 10^7 MM cells in 100 μl of RPMI 1640, together with 100 μl of Matrigel basement membrane matrix. When tumor was measurable, mice were assigned into four treatment groups receiving PS-341 or into a control group. Treatment with PS-341 was given i.v. twice weekly via tail vein at 0.05, 0.1, 0.5, and 1.0 mg/kg for 4 weeks. Subsequently, it was administered once weekly. The control group received the vehicle alone (0.9% sodium chloride) at the same schedule. Caliper measurements of the longest perpendicular tumor diameters were performed every alternate day to estimate the tumor volume, using the following formula: 4π/3 × (width/2)^2 × (length/2), representing the three-dimensional volume of an ellipse. Animals were sacrificed when their tumors reached 2 cm or when the mice became moribund. Survival was evaluated from the first day of treatment until death .

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

MG-341; PS-341; MLN341

Compound Identifiers

PubChem CID

387447