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BI-847325
本半岛bd体育手机客户端 不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。
BI-847325图片
CAS NO: 1207293-36-4
规格: ≥98%
包装与价格：
包装 价格(元)
5mg 电议
25mg 电议
50mg 电议
100mg 电议
250mg 电议
500mg 电议

半岛bd体育手机客户端 介绍
BI-847325 (BI847325) is a novel, potent, orally bioavailable, and selective dual inhibitor of MEK (mitogen-activated protein kinase kinase) and Aurora kinase with potential antitumor activity. It inhibits Aurora B, human Aurora A, Aurora C, MEK1 and MEK2 with IC50 of 3 nM, 25 nM, 15 nM, 25 nM, and 4 nM, respectively. BI 847325 shows potent in vitro antiproliferative activity and high in vivo antitumor efficacy.
理化性质和储存条件
Molecular Weight (MW) 464.56
Formula C29H28N4O2
CAS No. 1207293-36-4
Storage -20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility(In vitro) DMSO: 19 mg/mL (40.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility(In vivo) 2-hydroxyethyl cellulose, polysorbate 80 with pH adjusted to 2.8 with 1 M HCl: 30 mg/mL
Synonyms BI 847325; BI847325; BI-847325; (Z)-3-(3-((4-((dimethylamino)methyl)phenylamino)(phenyl)methylene)-2-oxoindolin-6-yl)-N-ethylpropiolamide
实验参考方法
In Vitro

In vitroactivity: BI-847325 shows growth-inhibitory effects on BRAF-mutant and vemurafenib-resistant melanoma cells with IC50 ranging from 0.3 nM to 2 μM, and prevents colony formation in six BRAF-mutant melanoma cell lines. BI-847325 also induces apoptosis by reducing Mcl-1 expression

Kinase Assay: BI-847325 is an ATP competitive dual inhibitor of MEK and aurora kinases (AK) with IC50 values of 15 and 4 nM for human AK-C and MEK2, respectively.

Cell Assay: Cells (M229, M229R, A375, A375R, WM793, WM793R, 1205Lu, 1205LuR, M249, M249R, WM164, WM164R, WM39 and RPMI17951 cells) are plated at a density of 2.5 × 103 cells per 100 μL and left to grow overnight before being treated with increasing concentrations of BI-847325 for 72 hours. The metabolic activity is determined using Alamar blue reagent as per the manufacturer's protocol.
In Vivo In mice bearing 1205Lu and 1205LuR xenografts, BI-847325 (75 mg/kg, p.o.) causes significant tumor suppression without significant alteration in the body weights
Animal model Mice bearing 1205Lu and 1205LuR xenografts
Formulation & Dosage Dissolved in 2-hydroxyethyl cellulose, polysorbate 80 with pH adjusted to 2.8 with 1 M HCl; 70 mg/kg; Oral gavage
References

Mol Cancer Ther. 2015 Jun;14(6):1354-64.
生物活性


The dual MEK and Aurora kinase inhibitor BI-847325 blocks the growth and survival of BRAF-mutant melanoma cell lines through induction of apoptosis. Mol Cancer Ther. 2015 Jun;14(6):1354-64.


BI-847325 induces apoptosis altering the expression of pro and anti-apoptotic proteins. Mol Cancer Ther. 2015 Jun;14(6):1354-64.


Decreased expression of Mcl-1 is required for BI-847325-mediated apoptosis. Mol Cancer Ther. 2015 Jun;14(6):1354-64.


BI-847325-mediated apoptosis is induced following downregulation of Mcl-1. Mol Cancer Ther. 2015 Jun;14(6):1354-64.


BI-847325 leads to decreased MEK expression in BRAF-mutant naive and vemurafenib-resistant cells. Mol Cancer Ther. 2015 Jun;14(6):1354-64.


BI-847325 inhibits growth of BRAF-mutant melanoma xenografts. Mol Cancer Ther. 2015 Jun;14(6):1354-64.
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