BIX 02189
BIX 02189 性质
| 沸点 | 653.4±55.0 °C(Predicted) |
|---|---|
| 密度 | 1.230±0.06 g/cm3(Predicted) |
| 储存条件 | 2-8°C(protect from light) |
| 溶解度 | DMSO:34.48(最大浓度 mg/mL);78.27(最大浓度 mM) DMF:15.0(最大浓度 mg/mL);34.05(最大浓度 mM) DMF:PBS ( pH 7.2) (1:1):0.5(最大浓度 mg/mL);1.13(最大浓度 mM) 乙醇:10.0(最大浓度 mg/mL);22.7(最大浓度 mM) |
| 形态 | 结晶固体 |
| 酸度系数(pKa) | 11.61±0.20(Predicted) |
| 颜色 | 白色至黄色 |
BIX 02189 用途与合成方法
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MEK5 1.5 nM (IC 50 ) |
ERK5 59 nM (IC 50 ) |
CSF1R (FMS) 46 nM (IC 50 ) |
LCK 250 nM (IC 50 ) |
JAK3 440 nM (IC 50 ) |
TGFβR1 580 nM (IC 50 ) |
RPS6KA6 (RSK4) 990 nM (IC 50 ) |
RPS6KA3 (RSK2) 2.1 μM (IC 50 ) |
FGFR1 1 μM (IC 50 ) |
KIT 1.1 μM (IC 50 ) |
ABL1 2.4 μM (IC 50 ) |
MAPK14 (p38 alpha) 3.7 μM (IC 50 ) |
SRC 7.6 μM (IC 50 ) |
BIX02189 blocks phosphorylation of ERK5, without affecting phosphorylation of ERK1/2 in sorbitol-stimulated HeLa cells. BIX02189 inhibits ERK5 phosphorylation in a dose dependent manner. Fluvastatin reduces advanced glycation endproduct (AGE)-induced vascular smooth muscle cells (VSMCs) proliferation. To confirm this effect, VSMCs are treated with AGEs in the presence or absence of Fluvastatin and then subject to MTT assay. AGEs are found to dose-dependently induce cell proliferation, and this is significantly suppressed by Fluvastatin. In addition to MTT assay, the similar results are got with cell counting. This suppressive effect of Fluvastatin is prevented when VSMCs are pretreated with BIX02189. Whether ERK5 activation can reduce proliferation is also examined by using Ad-CA-MEK5α encoding a constitutively active mutant form of MEK5α (an upstream kinase of ERK5). AGE-induced proliferation determined by both MTT assay and cell counting is significantly diminished in the presence of Ad-CA-MEK5α, and Nrf2 depletion using siRNA restored AGE-induced proliferation.
Mice are treated with either 10 mg/kg of BIX02189 (in 25% DMSO) or vehicle control (same volume of 25% DMSO) by intraperitoneal injection. The nuclear localization of Nrf2 is inhibited in aortic endothelial cells from mice treated with BIX02189.
