BI-847325
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
BI 847325是Ras丝裂原活化蛋白激酶激酶(MEK)和Aurora激酶的双重抑制剂[1,2]。BI 847325抑制MEK1和MEK2,IC50值分别为25和4 nM。BI 847325可抑制Aurora A、B和C的活性,IC50值分别为3、25和15 nM[1]。
RAS依赖性的MAP激酶信号传导通路在细胞存活和增殖的调节中至关重要。很难设计针对RAS蛋白的直接抑制剂。MEK是MAP激酶的下游激酶[1]。 MEK是ERK激酶[3]。
在BI 847325处理的细胞中,根据磷酸组蛋白H3(pHH3)和磷酸化ERK (pERK)的水平,确定了EC50值。在KRAS和PI3Kα突变体NCI-H460细胞中,EC50值是44 nM。对于BRAF突变体A375细胞中,EC50值是37 nM。在测试的来源于不同组织和不同基因背景的240个细胞系中,BI 847325强效的抑制细胞增殖,GI50值为28 nM。在一系列细胞系中,BI 847325诱导细胞死亡。这些体外效力与BRAF或RAS突变显著地相关[1]。
在皮肤黑素瘤(A375, BRAF突变体)和非小细胞肺癌(Calu-6, KRAS突变体)的裸鼠异种移植模型中,每日口服剂量为10 mg/kg的BI 847325完全抑制肿瘤生长。在A375肿瘤动物中,与对照组相比,BI 847325显著降低了肿瘤中pHH3和pERK [1]。
参考文献:
[1]. Sini P, Gürtler U, Zahn SK, et al. Pharmacological characterization of BI 847325, a dual inhibitor of MEK and Aurora kinases. Cancer Research, 2012, 72(8 Supplement): 1919-1919.
[2]. Hideshima T, Chauhan D, Richardson P, et al. NF-κB as a therapeutic target in multiple myeloma. Journal of Biological Chemistry, 2002, 277(19): 16639-16647.
[3]. Rommel C, Clarke BA, Zimmermann S, et al. Differentiation stage-specific inhibition of the Raf-MEK-ERK pathway by Akt. Science, 1999, 286(5445): 1738-1741..
Physical Appearance | A crystalline solid |
Storage | Store at -20°C |
M.Wt | 464.56 |
Cas No. | 1207293-36-4 |
Formula | C29H28N4O2 |
Solubility | ≥24.1 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O |
Chemical Name | (Z)-3-(3-(((4-((dimethylamino)methyl)phenyl)amino)(phenyl)methylene)-2-oxoindolin-6-yl)-N-ethylpropiolamide |
SDF | Download SDF |
Canonical SMILES | CCNC(C#CC1=CC=C2C(NC(/C2=C(NC3=CC=C(CN(C)C)C=C3)/C4=CC=CC=C4)=O)=C1)=O |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
质量控制和MSDS
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