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Sotrastaurin (AEB071)

现货
Catalog No.
A8525
PKC抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,350.00
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5mg
¥ 1,200.00
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10mg
¥ 1,800.00
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25mg
¥ 4,700.00
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50mg
¥ 8,500.00
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Background

AEB071 is an inhibitor of protein kinase C (PKC). The PKC inhibitor which can block the T-cell activation has the ability of immune suppression [1].

The protein kinase C (PKC) isoforms is very important in cell signaling, proliferation, differentiation, migration, survival, and death. PKC family has many isoforms. Among the PKC isoforms, PKC isoforms have basal effect on the T cells’ activation and other immune cell functions [2,3].

ABE071 is a potent inhibitor of novel and classical PKC isoforms. Through the inhibition of PKC, AEB071 can depress the activation and proliferation of T-cell and decrease the production of cytokine.ABE071 can also suppress the NK cell activity. Ex vivo stimulation of lymphocytes from subjects exposed to single doses of AEB071 resulted in a dose-dependent inhibition of both lymphocyte proliferation and IL2 mRNA expression

AEB071 is an effective treatment strategy for the cure of autoimmune diseases. According to the Psoriasis Area Severity Index (PASI) score, after 2 weeks’ treatment with 300 mg bid AEB071, Clinical severity of psoriasis was reduced up to 69% compared with baseline[2,3].

References:
[1].  Weckbecker G1, Pally C, Beerli C, et al. Effects of the novel protein kinase C inhibitor AEB071 (Sotrastaurin) on rat cardiac allograft survival using single agent treatment or combination therapy with cyclosporine, everolimus or FTY720. Transpl Int. 2010 May 1;23(5):543-52
[2].  Skvara H1, Dawid M, Kleyn E, Wolff B, et al. The PKC inhibitor AEB071 may be a therapeutic option for psoriasis. J Clin Invest. 2008 Sep;118(9):3151-9.
[3].   Matz M1, Weber U, Mashreghi MF, et al. Effects of the new immunosuppressive agent AEB071 on human immune cells. Nephrol Dial Transplant. 2010 Jul;25(7):2159-67

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt438.48
Cas No.425637-18-9
FormulaC25H22N6O2
SynonymsAEB 071;AEB-071
Solubility≥21.9mg/mL in DMSO
Chemical Name3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione
SDFDownload SDF
Canonical SMILESCN1CCN(CC1)C2=NC3=CC=CC=C3C(=N2)C4=C(C(=O)NC4=O)C5=CNC6=CC=CC=C65
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。

试验操作

激酶实验 [1]:

结合实验

通过闪烁亲和测定技术测定传统和新颖的PKC同种型。通过将1.5 μM的肽底物与10 μM [33P]ATP)、 10 mM Mg (NO3)2、0.2 mM CaCl2、25-400 ng/ml的PKC以及含有30mol%磷脂酰丝氨酸、5mol%二酰基甘油(DAG)和65mol%磷脂酰胆碱的脂质囊泡的最终浓度为0.5 μM的脂质孵育,在20 mM Tris-HCl缓冲液、pH7.4和0.1%牛血清白蛋白中进行测定。在室温下孵育60分钟。通过在不含Ca2+和Mg2+的PBS中加入50 μl含有100 mM EDTA、200 μM ATP、0.1%Triton X-100和0.375 μg/孔链霉素包被的闪烁亲近测定珠的混合物停止反应。在MicroBetaTrilux计数器中测量渗入的放射性1分钟。

细胞实验 [2]:

细胞系

GNAQ/GNA11突变Uveal黑色素瘤细胞系

溶解方法

该化合物在DMSO中的溶解度大于21.9 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

125-1000 nM,5天

应用

在GNAQ/GNA11突变体Uveal黑色素瘤细胞系中,AEB071抑制细胞增殖,主要是通过抑制PKC/ERK1/2途径。

动物实验 [2]:

动物模型

携带GNAQ突变异种移植物的SCID雌性裸鼠

给药剂量

口服,80 mg/kg/d,每天三次

应用

在GNAQ突变异种移植模型中,AEB071/BYL719组合使用抑制体内肿瘤生长。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Evenou J P, Wagner J, Zenke G, et al. The potent protein kinase C-selective inhibitor AEB071 (sotrastaurin) represents a new class of immunosuppressive agents affecting early T-cell activation[J]. Journal of Pharmacology and Experimental Therapeutics, 2009, 330(3): 792-801.

[2]. Musi E, Ambrosini G, De Stanchina E, et al. The phosphoinositide 3-kinase α selective inhibitor BYL719 enhances the effect of the protein kinase C inhibitor AEB071 in GNAQ/GNA11-mutant uveal melanoma cells[J]. Molecular cancer therapeutics, 2014, 13(5): 1044-1053.

生物活性

Description Sotrastaurin是蛋白激酶C(PKC)的高效选择性小分子抑制剂,其对PKCθ的Ki值为0.22 nM。
靶点 PKCθ          
IC50 0.22 nM          

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