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BX795

现货
Catalog No.
A8222
PDK1抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 850.00
现货
5mg
¥ 600.00
现货
10mg
¥ 1,100.00
现货
50mg
¥ 3,800.00
Ship with 10-15 days
100mg
¥ 5,000.00
Ship with 10-15 days

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Background

BX795, a small molecule with an aminopyrimidine backbone in its chemical structure, is a potent and ATP-competitive inhibitor of 3-phosphoinositide-dependent kinase 1 (PDK1) that binds to the ATP binding pocket of PDK1 and hence potently inhibits the enzymatic activity of PDK1 in a direct kinase assay format with a value of 50% concentration inhibition IC50 of 11 nM. BX795 is also a potent and selectively inhibitor of TANK-binding kinase 1 (TBK1) and IκB kinase ε (IKKε), with values of IC50 of 0.006 μM and 0.041 μM respectively, that blocks the phosphorylation, nuclear translocation and transcriptional activity of interferon regulatory factor 3 as well as the production of interferon-β in macrophages stimulated with poly(I:C) or lipopolysaccharide (LPS).

Reference

Feldman RI, Wu JM, Polokoff MA, Kochanny MJ, Dinter H, Zhu D, Biroc SL, Alicke B, Bryant J, Yuan S, Buckman BO, Lentz D, Ferrer M, Whitlow M, Adler M, Finster S, Chang Z, Arnaiz DO. Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J Biol Chem. 2005 May 20;280(20):19867-74.

Clark K, Plater L, Peggie M, Cohen P. Use of the pharmacological inhibitor BX795 to study the regulation and physiological roles of TBK1 and IkappaB kinase epsilon: a distinct upstream kinase mediates Ser-172 phosphorylation and activation. J Biol Chem. 2009 May 22;284(21):14136-46.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt591.48
Cas No.702675-74-9
FormulaC23H26IN7O2S
Solubility≥59.1mg/mL in DMSO with gentle warming, <2.48 mg/mL in EtOH, <2.09 mg/mL in H2O
Chemical NameN-[3-[[5-iodo-4-[3-(thiophene-2-carbonylamino)propylamino]pyrimidin-2-yl]amino]phenyl]pyrrolidine-1-carboxamide
SDFDownload SDF
Canonical SMILESC1CCN(C1)C(=O)NC2=CC=CC(=C2)NC3=NC=C(C(=N3)NCCCNC(=O)C4=CC=CS4)I
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]:

激酶实验

使用直接激酶测定法和耦合测定法(测定PDK1和PtdIns-3,4-P2介导的AKT2活化)测定PDK1。在耦合测定中,最终测定混合物 (60 μL) 含:15mM MOPS,pH 7.2,1 mg/mL牛血清白蛋白,18 mM β-甘油磷酸,0.7 mM二硫苏糖醇,3 mM EGTA,10 mM MgOAc,7.5 μM ATP,0.2 μCi [γ-33P]ATP,7.5 μM生物素化多肽底物(生物素化ARRRDGGGAQPFRPRAATF),0.5 μL含磷脂载体的PtdIns-3,4-P2,60 pg纯化的重组人PDK1,以及172 ng纯化的重组人AKT2。在室温下,孵育2小时后,在链霉亲和素包被的SPA珠上,10 μL测定混合物结合生物素标记的多肽。使用Wallac MicroBeta计数器,通过闪烁迫近分析法测定形成的产物。形成的产物与孵育时间以及加入的PDK1和失活AKT2数量成正比。在次优水平加入PDK1,使上述测定可以灵敏地检测AKT2的活化抑制剂以及PDK1或AKT2的直接抑制剂。为了直接测定PDK1活性,最终测定混合物 (60 μL) 含50 mM Tris-HCl,pH 7.5,0.1 mM EGTA,0.1 mM EDTA,0.1% β-巯基乙醇,1 mg/mL牛血清白蛋白,10 mM MgOAc,10 μM ATP,0.2 μCi of [γ-33P]ATP,7.5 μM底物肽 (H2N-ARRRGVTTKTFCGT) 和60 ng纯化的重组人PDK1。在室温下,4小时后,加入25 mM EDTA,在Whatman P81磷酸纤维素纸上点样。用0.75%磷酸冲洗滤纸3次,用丙酮冲洗1次。干燥后,使用富士磷光定量仪对过滤器结合的标记多肽进行定量分析。

细胞实验 [1]:

细胞系

MDA-468、HCT-116和MiaPaca细胞

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

~10 μM; 72 hrs

实验结果

在MDA-468、HCT-116和MiaPaca细胞中,BX795有效抑制肿瘤细胞生长,其IC50值分别为1.6、1.4和1.9 μM。

References:

[1]. Feldman RI, Wu JM, Polokoff MA, Kochanny MJ, Dinter H, Zhu D, Biroc SL, Alicke B, Bryant J, Yuan S, Buckman BO, Lentz D, Ferrer M, Whitlow M, Adler M, Finster S, Chang Z, Arnaiz DO. Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J Biol Chem. 2005 May 20;280(20):19867-74.

生物活性

描述 BX795是PDK1有效的、特异的抑制剂,IC50值为6 nM。
靶点 PDK1          
IC50 6 nM          

质量控制

化学结构

BX795

相关生物数据

BX795

相关生物数据

BX795