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PCI-32765 (Ibrutinib)Bruton's tyrosine kinase (BTK)抑制剂

PCI-32765 (Ibrutinib)

产品编号:A3001
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规格 单价 库存 订购数量
10mM (in 1mL DMSO) ¥550.00 现货
5mg ¥560.00 现货
10mg ¥800.00 现货
50mg ¥2,400.00 现货
200mg ¥4,500.00 现货

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Sample solution is provided at 25 µL, 10mM.

引用文献

1. Alhakeem SS, McKenna MK, et al. "Chronic Lymphocytic Leukemia-Derived IL-10 Suppresses Antitumor Immunity." J Immunol. 2018 Jun 15;200(12):4180-4189. PMID:29712773
2. Schroeder JT, Bieneman AP. "Activation of Human Basophils by A549 Lung Epithelial Cells Reveals a Novel IgE-Dependent Response Independent of Allergen." J Immunol. 2017 Aug 1;199(3):855-865. PMID:28652400
3. Kosowicz JG, Lee J, et al. "Drug modulators of B cell signaling pathways and Epstein-Barr virus lytic activation." J Virol. 2017 May 31. pii: JVI.00747-17. PMID:28566383
4.Lee DD, Muskaj I, et al. "Platelet proteins cause basophil histamine release through an immunoglobulin-dependent mechanism. Transfusion." 2017 May 4. PMID:28470742

质量控制

化学结构

PCI-32765 (Ibrutinib)

相关生物数据

PCI-32765
In the Burkitt lymphoma cell line Namalwa, the anti-IgM–induced phosphorylation of protein kinase B (PKB/AKT) and ERK were inhibited by PCI-32765 , whereas phosphorylation of the activating LYN/SYK substrate site Y551 of BTK was actually upregulated.

Review (University of Minnesota)

PCI-32765
Fura-2 loaded purified basophils were incubated with vehicle control (0.0005% DMSO) or 50 nM PCI-32765 for 10 minutes prior to the addition of 0.5 μg/ml anti-IgE antibody and the cytosolic calcium response monitored. The 350/380 excitation ratio is plotted for the average of two experiments.

Review (Thomas Jefferson University)

PCI-32765
Src expression in BMMs cultured with RANKL and M-CSF for 3 days in the presence of ibrutinib at indicated concentration.

相关生物数据

PCI-32765

相关生物数据

PCI-32765

相关生物数据

PCI-32765

相关生物数据

PCI-32765

PCI-32765 (Ibrutinib) Dilution Calculator

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化学性质

CAS号 936563-96-1 SDF Download SDF
别名 PCI-32765,Ibrutinib,CRA-032765
化学名 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide
SMILES C=CC(=O)N1CCCC(C1)N2C3=C(C(=N2)C4=CC=C(C=C4)OC5=CC=CC=C5)C(=NC=N3)N
分子式 C25H24N6O2 分子量 440.5
溶解度 ≥22.025mg/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 Ibrutinib是一种有效的、高选择性的Bruton's tyrosine kinase (BTK)抑制剂,IC50值为0.5 nM,对Bmx、CSK、 FGR、 BRK及HCK中度有效,对EGFR、Yes、ErbB2、JAK3等作用效果较弱。
靶点 Btk          
IC50 0.5 nM          

实验操作

细胞实验:

细胞系

CLL细胞系

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 μM;24 h、48 h和72 h

应用

在CLL细胞中,PCI-32765处理24 h、48 h和72 h后均减少anti-IgM支持的细胞活力,从69%分别减少到33%、31%和29%。与非刺激对照相比,anti-IgM刺激24 h后诱导细胞活力平均增加27%±12%。而与非刺激对照相比,在anti-IgM刺激之前,用1 μM PCI-32765处理显著减少CLL细胞的活力到98%±8%。PCI-32765也可以有效抑制来自NLCs的存活信号。

动物实验:

动物模型

CB17 SCID小鼠和Eμ-TCL1转基因(Tg)C3H/BL6小鼠

剂量

次优(2.5 mg/kg/d);最佳(25 mg/kg/d)

应用

在过继转移TCL1小鼠模型中,细胞转移两周后分别用次优(2.5 mg/kg/d)和最佳(25 mg/kg/d)剂量的PCI-32765处理,小鼠在第4天出现瞬态淋巴细胞增多,并分别增加了7倍和10倍的循环TCL1白血病细胞。

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] Ponader S, Chen S S, Buggy J J, et al. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo[J]. Blood, 2012, 119(5): 1182-1189.

研究更新

1. Ibrutinib (PCI-32765) in chronic lymphocytic leukemia. Hematol Oncol Clin North Am. 2013 Aug;27(4):851-60, x. doi: 10.1016/j.hoc.2013.01.006.
Abstract
PCI-32765, an inhibitor of Bruton tyrosine kinase, has the potential to be an integral component of CLL therapy for its inhibition against CLL cell survival and proliferation and its impacts on CLL cell migration and homing.
2. [Effect of PCI-32765 and bortezomib on proliferation and apoptosis of B-cell tumor cell lines and its mechanisms]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013 Oct;21(5):1178-82. doi: 10.7534/j.issn.1009-2137.2013.05.018.
Abstract
PCI-32765, a Btk inhibitor, dose- and time- dependently inhibited proliferation and significantly induced apoptosis in Raji and Ramos cells; while the combination of PCI-32765 and bortezomib synergistically enhanced those effects with down-regulation of Btk, NFKB, Bcl-cl and c-IAP1 and up-regulation of caspase-3.
3. The Bruton tyrosine kinase (BTK) inhibitor PCI-32765 synergistically increases proteasome inhibitor activity in diffuse large-B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cells sensitive or resistant to bortezomib. Br J Haematol. 2013 Apr;161(1):43-56. doi: 10.1111/bjh.12206. Epub 2013 Jan 30.
Abstract
The combination of PCI-32765 and bortezomib increased mitochondrial injury, apoptosis and ROS generation in DLBCL and MCL cells with minimal toxicity towards normal CD34(+) bone marrow cells.
4. The orally available Btk inhibitor ibrutinib (PCI-32765) protects against osteoclast-mediated bone loss. Bone. 2014 Mar;60:8-15. doi: 10.1016/j.bone.2013.11.025. Epub 2013 Dec 4.
Abstract
PCI-32765 inhibits both osteoclast differentiation and function leading to suppressed osteoclastic bone resorption, where it downregulates NFATc1 expression and disrupts the actin ring formation in mature osteoclasts. PCI-32765 also alleviated bone loss in an osteoporosis mouse model.

产品描述

PCI-32765 (Ibrutinib)是Bruton tyrosine kinase(BTK)的抑制剂,被用于研究BTK对成熟B细胞功能和B细胞相关疾病发展的生物学效应。BTK是BCR信号所必须的。人和小鼠中扰乱BTK功能的突变可以阻止B细胞的成熟,而B细胞的成熟需要功能性BCR途径的参与。PCI-32765还可以抑制自身抗体的产生。在体外和体内试验中,通过使用BTK亲和性的荧光探针检测到PCI-32765占据了BTK的活性位点。

参考文献:
1. Lee A. Honigberga, Ashley M. Smitha, Mint Sirisawada, Erik Vernera, David Lourya, Betty Changa, Shyr Lib, Zhengying Panb,d, Douglas H. Thamme, Richard A. Millera, and Joseph J. Buggya. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. PNAS. 2010; 107(29): 13075 – 80.