Bortezomib

製品コードS1013 バッチS101319

印刷

化学情報

Chemical Structure Synonyms LDP-341, MLM341, NSC 681239,PS-341 Storage
(From the date of receipt)		 3 years-20°C （in the dark）powder
化学式

C19H25BN4O4
分子量 384.24 CAS No. 179324-69-7
Solubility (25°C)* 体外 DMSO 77 mg/mL (200.39 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO 40%PEG 300 5%Tween80 50% ddH2O
2.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 40 mg/mL clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify; add 50 μL of Tween-80 to the above system, mix evenly to clarify; Then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 ボルテゾミブ (Bortezomib (PS-341, LDP-341, MLM341, NSC 681239)) は強力な 20S プロテアソーム (20S proteasome) 阻害剤であり、Ki は 0.6 nM です。正常細胞に比べがん細胞に対してより高い選択性を示します。 ボルテゾミブ (PS-341) は NF-κB を阻害し ERK のリン酸化を誘導することにより、卵巣がんなどの固形腫瘍において カテプシンB (cathepsin B) を抑制し、オートファジー (autophagy) の分解過程を阻害します。
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 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. [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]

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 Human multiple myeloma cells line U266
濃度 ~10 μM
反応時間 2 days
実験の流れ

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.
動物実験 動物モデル Human plasmacytoma xenografts RPMI 8226
投薬量 1 mg/kg
投与方法 i.v. twice weekly for 4 weeks, then once weekly

カスタマーフィードバック

Data from [Data independently produced by Sci Transl Med, 2015, 6(250), 250ra112]

Data from [Data independently produced by Cancer Res, 2015, 75(8), 1714-24]

Data from [Data independently produced by J Clin Invest, 2014, 124(9), 3757-66]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Combined KRAS-MAPK pathway inhibitors and HER2-directed drug conjugate is efficacious in pancreatic cancer [ Nat Commun, 2024, 15(1):2503] PubMed: 38509064
hnRNPA2B1 represses the disassembly of arsenite-induced stress granules and is essential for male fertility [ Cell Rep, 2024, 43(2):113769] PubMed: 38363675
Targeting of mitochondrial fission through natural flavanones elicits anti-myeloma activity [ J Transl Med, 2024, 22(1):208] PubMed: 38413989
Electrophilic MiniFrags Revealed Unprecedented Binding Sites for Covalent HDAC8 Inhibitors [ J Med Chem, 2024, 67(1):572-585] PubMed: 38113354
A novel T cell-redirecting anti-GPRC5D × CD3 bispecific antibody with potent antitumor activity in multiple myeloma preclinical models [ Sci Rep, 2024, 14(1):5135] PubMed: 38429446
RNF125‑mediated ubiquitination of MCM6 regulates the proliferation of human liver hepatocellular carcinoma cells [ Oncol Lett, 2024, 27(3):105] PubMed: 38298426
Bortezomib modulated the autophagy-lysosomal pathway in a TFEB-dependent manner in multiple myeloma [ Leuk Res, 2024, 138:107455] PubMed: 38368721
Expression of the chemokine receptor CCR1 decreases sensitivity to bortezomib in multiple myeloma cell lines [ Leuk Res, 2024, 139:107469] PubMed: 38479337
C. elegans RIG-I-like receptor DRH-1 signals via CARDs to activate anti-viral immunity in intestinal cells [ bioRxiv, 2024, 2024.02.05.578694] PubMed: 38370651
Novel Anti-B-cell Maturation Antigen Alpha-Amanitin Antibody-drug Conjugate HDP-101 Shows Superior Activity to Belantamab Mafodotin and Enhanced Efficacy in Deletion 17p Myeloma Models [ Res Sq, 2024, rs.3.rs-3843028] PubMed: 38260385

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