BIX02189 is a potent and selectiveMEK5inhibitor with anIC₅₀of 1.5 nM. BIX02189 also inhibitsERK5catalytic activity with anIC₅₀of 59 nM.

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^[1]. 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^[2].

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^[3].

440.54

Solid

C₂₇H₂₈N₄O₂

1265916-41-3

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 49.4 mg/mL(112.14 mM)

*"≥" means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 2.5 mg/mL (5.67 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.67 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20%SBE-β-CDin saline)

  Solubility: ≥ 2.5 mg/mL (5.67 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.67 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 2.5 mg/mL (5.67 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.67 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。