产品说明书

Bortezomib

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Chemical Structure| 179324-69-7 同义名 : PS-341;LDP-341;MLN 341. US brand name: VELCADE.;MLN341;MG-341;NSC 681239
CAS号 : 179324-69-7
货号 : A385479
分子式 : C19H25BN4O4
纯度 : 98%
分子量 : 384.24
MDL号 : MFCD09056737
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(130.13 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

无水乙醇: 60 mg/mL(156.15 mM)，配合低频超声，并水浴加热至45℃助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 11 mg/mL clear

PO 0.5% CMC-Na 30 mg/mL suspension

生物活性
靶点

  • 20S proteasome

    20S proteasome, Ki:0.6 nM
描述 The proteasome is a catalytic enzyme complex responsible for the degradation of intracellular proteins. Bortezomib is a dipeptide boronate that potently inhibits proteasome with a Ki value of 0.6 nM. After 48-hour incubation, bortezomib at 0.1 μM completed inhibited the growth of different human multiple myeloma (MM) cell lines, including U266, IM-9 and Hs Sultan cells. In U266 and patient primary MM cells, the treatment of 0.01 μM bortezomib induced a progressive increase of sub-G0/G1 phase cells in a time-dependent manner from 0 – 16h. Apoptosis as indicated by DNA fragmentation was also promoted by bortezomib treatment. H460 cells treated by 0.01 – 10 μM bortezomib for 24 hours showed increased cell accumulation at G2-M phase and cell apoptosis in a dose-dependent manner compared to control cells. Bortezomib treatment also led to concentration-dependent phosphorylation of Bcl-2 proteins. When cells were exposed to higher doses of bortezomib (0.1 – 10 μM) for 24 hours, the superphosphorylated form of Bcl-2 was detected. After the exposure to 0.01 – 0.05 μM bortezomib for 24 hours, or 0.1 μM bortezomib for 12 hours, the first cleavage fragment of Bcl-2 protein was detected. The second cleave fragment of Bcl-2 was only found in cells treated with 0.1 μM bortezomib for 12 hours. After incubating with 0.1 μM bortezomib for 24 hours, the phosphorylated Bcl-2 bands were observed in both Triton-X-100 soluble and insoluble fraction. In vivo study showed that 3 times per week injection of 2 mg/kg bortezomib for 25 days inhibited the growth of murine and human squamous cell carcinoma in mice.
作用机制 Bortezomib inhibits proteasome by reversibly binding to the chymotrypsin-like subunit of the proteasome.
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
697 Growth Inhibition Assay IC50=1.99 nM SANGER
8-MG-BA Growth Inhibition Assay IC50=0.25 nM SANGER
A101D Growth Inhibition Assay IC50=0.225 nM SANGER
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00571493 Non-hodgkin's Lymphoma ... 展开 >> Mantle Cell Lymphoma 收起 << Phase 1 Phase 2 Completed - United States, Nebraska ... 展开 >> University of Nebraska Medical Center, Section of Oncology/Hematology Omaha, Nebraska, United States, 68198-7680 收起 <<
NCT00580320 Melanoma Soft... 展开 >> Tissue Sarcoma Parathyroid Carcinoma Small Cell Carcinoma of the Lung Carcinoid Tumors 收起 << Phase 1 Completed - United States, New Hampshire ... 展开 >> Dartmouth Hitchcock Medical Center Lebanon, New Hampshire, United States, 03756 United States, Virginia Massey Cancer Center/Virginia Commonwealth University Richmond, Virginia, United States, 23298 收起 <<
NCT02808091 Extranodal NK-T-CELL LYMPHOMA Phase 2 Terminated(Slow recruitment) - Singapore ... 展开 >> National Cancer Centre Singapore, Singapore, 169610 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.60mL

0.52mL

0.26mL

13.01mL

2.60mL

1.30mL

26.03mL

5.21mL

2.60mL
参考文献

[1]Ludwig H, Khayat D, et al. Proteasome inhibition and its clinical prospects in the treatment of hematologic and solid malignancies. Cancer. 2005;104(9):1794-807.

[2]Hideshima T, Richardson P, et al. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res. 2001;61(7):3071-6.

[3]Ling YH, Liebes L, et al. PS-341, a novel proteasome inhibitor, induces Bcl-2 phosphorylation and cleavage in association with G2-M phase arrest and apoptosis. Mol Cancer Ther. 2002;1(10):841-9.

[4]Sunwoo JB, Chen Z, et al. Novel proteasome inhibitor PS-341 inhibits activation of nuclear factor-kappa B, cell survival, tumor growth, and angiogenesis in squamous cell carcinoma. Clin Cancer Res. 2001;7(5):1419-28.

[5]Accardi F, Toscani D, et al. Mechanism of Action of Bortezomib and the New Proteasome Inhibitors on Myeloma Cells and the Bone Microenvironment: Impact on Myeloma-Induced Alterations of Bone Remodeling. Biomed Res Int. 2015.