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BKM120I类PI3K抑制剂

BKM120

产品编号:A3015
ApexBio 的所有产品仅用作科研,我们不为任何个人用途提供产品和服务
规格 单价 库存 订购数量
10mM (in 1mL DMSO) ¥750.00 现货
5mg ¥900.00 现货
10mg ¥1,500.00 现货
100mg ¥5,800.00 现货

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Sample solution is provided at 25 µL, 10mM.

引用文献

1. Peng T, Dou QP. "Everolimus Inhibits Growth of Gemcitabine-Resistant Pancreatic Cancer Cells via Induction of Caspase-Dependent Apoptosis and G(2) /M Arrest." J Cell Biochem. 2017 Feb 6. PMID:28165150

质量控制

化学结构

BKM120

相关生物数据

BKM120
Annexin V assay analyzing stages of apoptosis 48 h following drug treatments [BKM120 (2 μM)] for U87Mg cells; Experiments were repeated 3 times. The mean ± SEM from at least 2–3 independent experiments containing 4 replicates each were obtained. Students t test was used to determine significance (p < 0.05) between groups. AV annexin V, PI propidium iodide.

相关生物数据

BKM120
BKM120 almost completely blocked the phosphorylation of Akt at concentration of 2.5 μM. High concentrations of BKM120 such as 5 μM and 10 μM induced cell death.
Method:Western Blot; Cell Lines:Primary HUVECs; Concentrations:2.5 μM; Incubation Time:2 h.

相关生物数据

BKM120

BKM120 Dilution Calculator

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化学性质

CAS号 944396-07-0 SDF Download SDF
别名 BKM-120,Buparlisib,BKM 120,NVP-BKM120,NVP-BKM-120
化学名 5-(2,6-dimorpholin-4-ylpyrimidin-4-yl)-4-(trifluoromethyl)pyridin-2-amine
SMILES C1COCCN1C2=NC(=NC(=C2)C3=CN=C(C=C3C(F)(F)F)N)N4CCOCC4
分子式 C18H21F3N6O2 分子量 410.39
溶解度 ≥20.52mg/mL in DMSO 储存条件 Store 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 BKM120是一种选择性的PI3K抑制剂,作用于p110α/β/δ/γ,IC50值分别为52 nM/166 nM/116 nM/262 nM。
靶点 p110α p110β p110δ p110γ    
IC50 52-99 nM 166 nM 116 nM 262 nM    

实验操作

细胞实验[1]:

细胞系

MM细胞系(RPMI-8226、OPM1、MM.1S、OPM2和H929)。

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

48小时;IC50: 0.5-1 μM。

应用

用MTT实验检测逐渐增加浓度的buparlisib介导的pan-PI3K抑制对MM细胞存活的效应。在所有检测的MM细胞系中,buparlisib处理48小时后诱导细胞毒性,IC50值介于0.5-1 μM之间。此外,在MM.1S细胞中,buparlisib以剂量依赖的方式减少PI3K下游信号蛋白的激活,包括pAkt、pS6R、pP70S6K和p-mTOR。

动物实验[1]:

动物模型

注射MM.1S-GFP+/luc+细胞的雌性SCID-Bg小鼠

剂量

50 mg/kg,2次/天,5周;口服给药。

应用

与对照组相比,buparlisib治疗后显著减少小鼠中肿瘤发展的速率。该结果进一步通过荧光显微镜证实,与对照组相比,buparlisib治疗小鼠的骨髓(BM)中存在的MM.1S- GFP+/luc+细胞的数量显著减少。

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] Sahin I, Azab F, Mishima Y, Moschetta M, Tsang B, Glavey SV, Manier S, Zhang Y, Sacco A, Roccaro AM, Azab AK, Ghobrial IM. Targeting survival and cell trafficking in multiple myeloma and Waldenstrom macroglobulinemia using pan-class I PI3K inhibitor, buparlisib. Am J Hematol. 2014 Jul 24.

研究更新

1. Effects of PI3K inhibitor NVP-BKM120 on acquired resistance to gefitinib of human lung adenocarcinoma H1975 cells. J Huazhong Univ Sci Technolog Med Sci. 2013 Dec;33(6):845-51. doi: 10.1007/s11596-013-1209-5. Epub 2013 Dec 13.
Abstract
NVP-BKM120, a class I PI3K inhibitor, concentration-dependently inhibited the growth of H1975 cells, which increased the proportion of H1975 cells in G0-G1 phase at 1 umol/L and promoted apoptosis at 2 umol/L. Moreover, NVP-BKM120 overcame acquired gefitinib resistance in H1975 cells though down-regulation of phosphorylated protein in PI3K/AKT signal pathways, including Akt, S6 and 4E-BP1.
2. The phosphatidylinositol-3-kinase inhibitor NVP-BKM120 overcomes resistance signals derived from microenvironment by regulating the Akt/FoxO3a/Bim axis in chronic lymphocytic leukemia cells. Haematologica. 2013 Nov;98(11):1739-47. doi: 10.3324/haematol.2013.088849. Epub 2013 Jul 12.
Abstract
NVP-BKM120 is an orally-available inhibitor of class I phosphatidylinositol-3-kinase that promoted mitochondrial apoptosis in chronic lymphocytic leukemia primary cells through blocking phosphatidylinositol-3-kinase signaling, decreasing Akt and FoxO3a phosphorylation and inducing Bim expression. NVP-BKM120 disrupts phosphatidylinositol-3-kinase pathway in chronic lymphocytic leukemia primary cells by inhibiting microenvironment signals, including B-cell receptor- and stroma-dependent Akt pathway activation, B-cell receptor stimulation induced chemokines secretion and CXCL12 triggered cell chemotaxis and actin polymerization upon CXCR4.
3. Inhibition of pan-class I phosphatidyl-inositol-3-kinase by NVP-BKM120 effectively blocks proliferation and induces cell death in diffuse large B-cell lymphoma. Leuk Lymphoma. 2014 Feb;55(2):425-34. doi: 10.3109/10428194.2013.806800. Epub 2013 Jul 25.
Abstract
Inhibition of PI3K/Akt/mammalian target of mTOR signaling pathway by NVP-BKM120, a pan-class I PI3K inhibitot, in DLBCL cells results in decreased cell proliferation, increased apoptotic cell death, increased expression of Puma and Bim and down-regulation of Bcl-xL and Mcl-1.
4. The PI3 kinase inhibitor NVP-BKM120 induces GSK3/FBXW7-dependent Mcl-1 degradation, contributing to induction of apoptosis and enhancement of TRAIL-induced apoptosis. Cancer Lett. 2013 Sep 28;338(2):229-38. doi: 10.1016/j.canlet.2013.03.032. Epub 2013 Apr 2.
Abstract
BKM120, a PI3 kinase inhibitor, induced apoptosis and enhanced TRAIL-induced apoptosis in human lung cancer cells through facilitating Mcl-1 degradation involving a GSK3/FBXW7-dependent mechanism.
5. Activity of the pan-class I phosphoinositide 3-kinase inhibitor NVP-BKM120 in T-cell acute lymphoblastic leukemia. Leukemia. 2013 Nov 6. doi: 10.1038/leu.2013.369. [Epub ahead of print]
Abstract
BKM120, an orally-available pan-PI3K inhibitor, has the potential to treat T-ALL for its abilities to induce G2/M phase cell cycle arrest and apoptosis T-ALL cells and patient T lymphoblasts, significantly delay tumor growth in a subcutaneous xenotransplant model of human T-ALL and synergize with chemotherapeutic agents for treating T-ALL patients.

产品描述

BKM120是I类PI3K的小分子抑制剂,特异性地抑制p110α、p110β、p110γ和p110δ,IC50值分别为52 nM、166nM、262nM和116 nM。在癌症中,PI3K-AKT-mTOR途径是抑制肿瘤生长,诱导细胞死亡的一条关键细胞内信号通路。在缺乏PTEN的癌细胞中,BKM120减少下游效应因子AKT的磷酸化,从而抑制肿瘤细胞增殖,诱导G1期细胞周期阻滞和细胞凋亡。

参考文献:
1.  Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. JC Bendell, J Rodon, HA Burris. Journal of Clinical Oncology. 2012
2.  Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. SM Maira, S Pecchi, A Huang, M Burger, M Knapp. Molecular cancer Therapeutics. 2012