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Carfilzomib (PR-171)蛋白酶体抑制剂

Carfilzomib (PR-171)

产品编号:A1933
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规格 单价 库存 订购数量
10mM (in 1mL DMSO) ¥1,500.00 现货
5mg ¥1,050.00 现货
10mg ¥1,330.00 现货
25mg ¥2,200.00 现货

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Sample solution is provided at 25 µL, 10mM.

引用文献

质量控制

化学结构

Carfilzomib (PR-171)

相关生物数据

Carfilzomib
Synchronous trophozoites were treated with 100 nM or 1μ M carfilzomib for the indicated times followed by inhibitor wash out. Parasites were placed in fresh media, and proteasome activities of all samples were determined by MV151 labeling at 10 hr after inhibitor washout. Quantification of the putative β5 subunit labeling is shown in the graph below the gel image.

相关生物数据

Carfilzomib (PR-171)

相关生物数据

Carfilzomib (PR-171)

相关生物数据

Carfilzomib (PR-171)

相关生物数据

Carfilzomib (PR-171)

相关生物数据

Carfilzomib (PR-171)

相关生物数据

Carfilzomib (PR-171)

Carfilzomib (PR-171) Dilution Calculator

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化学性质

CAS号 868540-17-4 SDF Download SDF
别名 PR 171,PR171,PR-171,Carfilzomib
化学名 (2S)-4-methyl-N-[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]-4-phenylbutanoyl]amino]pentanamide
SMILES CC(C)CC(C(=O)C1(CO1)C)NC(=O)C(CC2=CC=CC=C2)NC(=O)C(CC(C)C)NC(=O)C(CCC3=CC=CC=C3)NC(=O)CN4CCOCC4
分子式 C40H57N5O7 分子量 719.91
溶解度 ≥36.0mg/mL in DMSO 储存条件 Desiccate at -20°C
物理性状 A solid 运输条件 试用装:蓝冰运输。
其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议 为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

生物活性

描述 Carfilzomib (PR-171)是一种不可逆的蛋白酶体抑制剂,IC50 < 5 nM。
靶点 Proteasome          
IC50 5 nM          

实验操作

细胞实验[1]:

细胞系

HT-29结肠腺癌细胞

溶解方法

在DMSO中的溶解度>10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

1 h;IC50 = 9 nM

应用

HT-29结肠腺癌细胞与PR-171孵育1 h可导致所有三个蛋白酶体催化活性的剂量依赖性抑制,其中胰凝乳蛋白酶样活性具有最大的敏感性(IC50 = 9 nM)。与分离酶实验相比(IC50>1 μM),细胞实验中caspase样和胰蛋白酶样活性可以更大程度地被抑制(IC50=150–200 nM)。

动物实验[1]:

动物模型

BNX小鼠

剂量

5 mg/kg/周,连续两天(QDx2);静脉注射

应用

在人肿瘤异种移植BNX小鼠中评估PR-171的抗肿瘤活性,异种移植物源自三个肿瘤细胞系,分别是HT-29(结肠腺癌)、RL(B细胞淋巴瘤)和HS-Sultan(伯基特氏淋巴瘤)。所有的PR-171给药方案(高达5 mg/kg,QDx2)在荷瘤动物中均具有耐受性,体重下降小于10%。结果表明,PR-171的活性是剂量和给药方案依赖的。PR-171也可以抑制血液和肾上腺中蛋白酶体的活性。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Demo S D, Kirk C J, Aujay M A, et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome[J]. Cancer research, 2007, 67(13): 6383-6391.

研究更新

1. Carfilzomib: a novel agent for multiple myeloma. J Pharm Pharmacol. 2013 Aug;65(8):1095-106. doi: 10.1111/jphp.12072. Epub 2013 Apr 24.
Abstract
Carfilzomib has been review as a new agent to treat relapsed and refractory MM.
2. A novel Bruton's tyrosine kinase inhibitor CC-292 in combination with the proteasome inhibitor carfilzomib impacts the bone microenvironment in a multiple myeloma model with resultant anti-myeloma activity. Leukemia. 2014 Feb 12. doi: 10.1038/leu.2014.69. [Epub ahead of print]
Abstract
Instead of inhibiting the formation of OC sealing zone alone, the combination of cartfilzomib and CC-292 exhibited synergistic anti-MM activities, including inhibition of both sealing zone formation and differentiation of OC, suppression of tumor burden in a mouse model and increasing bone volume.
3. In vitro and in vivo therapeutic efficacy of carfilzomib in mantle cell lymphoma: targeting the immunoproteasome. Mol Cancer Ther. 2013 Nov;12(11):2494-504. doi: 10.1158/1535-7163.MCT-13-0156. Epub 2013 Aug 29.
Abstract
Carfilzomib, a proteasome inhibitor, is an anti-MCL agent that concentration-dependently inhibited cell growth, induced apoptosis and suppressed survival signaling pathways NF-KB and STAT3 without causing toxicity to normal peripheral blood mononuclear cells. Immunoproteasome, particularly LMP2, plays an indispensible role in anti-MCL activity of carfilzomib.
4. Carfilzomib-Associated Tumor Lysis Syndrome. Pharmacotherapy. 2014 Jan 4. doi: 10.1002/phar.1397. [Epub ahead of print]
Abstract
Even though it is an FDA-approved anti-MM drug with less than 1% TLS frequency, carfilzomib has been associated with TLS development in a 55-year-old male patient with relapsed MM.
5. Carfilzomib: a second-generation proteasome inhibitor for the treatment of relapsed and refractory multiple myeloma. Ann Pharmacother. 2013 Jan;47(1):56-62. doi: 10.1345/aph.1R561. Epub 2013 Jan 8.
Abstract
Carfilzomib, an FDA-approved anti-MM drug, has been evaluated in the treatment of patients who have relapsed and refractory MM and received prior bortezomib and thalidomide or lenalidomide.

产品描述

Carfilzomib (PR-171)是环氧酶素(epoxomicin)的衍生物,具有潜在的抗肿瘤活性。Carfilzomib不可逆的结合并抑制20S蛋白酶体的胰凝乳蛋白酶样活性。20S蛋白酶体负责降解大量的细胞内蛋白。抑制蛋白酶体介导的蛋白水解可以引起聚泛素化蛋白的积累,从而导致细胞周期停滞、诱导细胞凋亡和抑制肿瘤生长。

参考文献:
1.  Guido Cavaletti, et al., Leukemia & Lymphoma (2010), 51(7), 1178-1187. 2. Girija Dasmahapatra, et al., Blood (2010), 115(22), 4478-4487.