1207293-36-4BI-847325

产品属性：

Cas No.1207293-36-4

别名

化学名 (Z)-3-(3-(((4-((dimethylamino)methyl)phenyl)amino)(phenyl)methylene)-2-oxoindolin-6-yl)-N-ethylpropiolamide

分子式 C29H28N4O2

分子量 464.56

溶解度 DMF: 16 mg/ml,DMF:PBS(pH 7.2)(1:6): 0.14 mg/ml,DMSO: 5 mg/ml,Ethanol: 0.3 mg/ml

储存条件 Store at -20°C
General tips  For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping Condition     Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
产品描述：
The RAS-dependent MAP kinase signaling pathway is important in the regulation of cell survival and proliferation. It is hard to design direct inhibitors of RAS proteins. MEK is a downstream kinase of MAP kinase [1]. MEK is a ERK kinase [3].

In cells treated with BI 847325, based on levels of phospho-histone H3 (pHH3) and phospho-ERK (pERK), EC50 values were determined. To KRAS-and-PI3Kα-mutant NCI-H460 cells, the EC50 value was 44 nM. To BRAF-mutant A375 cells, the EC50 value was 37 nM. In a panel of 240 cell lines from diverse tissues with diverse genetic background, BI 847325 produced a potent inhibition of cell proliferation with a gm GI50 value of 28 nM. In a subset of cell lines, BI 847325 induced cell death. These in vitro potency correlated with mutations in BRAF or RAS, significantly [1].

In nude mouse xenograft models of cutaneous melanoma (A375, mutant BRAF) and NSCLC (Calu-6, mutant KRAS), BI 847325 at a daily oral dose of 10 mg/kg produced complete inhibition of tumor growth. In animals with A375 tumors, treatment with BI 847325 significantly reduced levels of both pHH3 and pERK in the tumors compared to controls [1].

References:

[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..