BIX02188 is a potentMEK5-selective inhibitor with anIC₅₀of 4.3 nM. BIX02188 inhibitsERK5catalytic activity, with anIC₅₀of 810 nM.

BIX02188 is a potent inhibitor of catalytic function of purified, active MEK5 enzyme. In activated HeLa cells, BIX02188 blocks phosphorylation of ERK5, without affecting phosphorylation of ERK1/2, JNK and p38 MAP kinases. To characterize the effects of BIX02188 in cultured endothelial cells (EC), H₂O₂is used to activate BMK1. Bovine lung microvascular endothelial cells (BLMECs) are pretreated with 0.1-10 μM BIX02188 for 30 min, and then stimulated with 300 μM H₂O₂. BMK1 is dramatically activated by H₂O₂, with peak at 20 min. Phosphorylated BMK1 is inhibited by BIX02188 in a dose-dependent manner, with an IC₅₀=0.8±1.0 μM, and maximal inhibition at concentrations >3 μM. To examine the specificity of BIX02188, The effect of 0.1-10 μM BIX02188 is measured on the activity of ERK1/2 and JNK. There is no significant inhibition of ERK1/2 and JNK at these concentrations. These observations confirm the selectivity of BIX02188 for MEK5-induced BMK1 phosphorylation^[1]. BIX02188 inhibits MEK5 and ERK5 activity, with IC₅₀s of 4.3 nM and 810 nM, respectively. BIX02188 does not inhibit closely related kinases MEK1, MEK2, ERK2, and JNK2. BIX02188 inhibits ERK5 phosphorylation in a dose dependent manner^[2]. To assess the proliferation of podocytes in response to the pro-fibrotic stimulus of TGFβ1, podocytes are pre-incubated in the presence and absence of BIX02188 (10 μM) for 60 min after which cells are co-treated with TGFβ1 (2.5 ng/mL) for 48 h to provide adequate time for proliferation to occur and a colorimetric cell proliferation assay is employed where metabolic activity is directly proportional to cell number. Inhibition of Erk5 activation with BIX02188 incubation reduces podocyte cell number. TGFβ1 stimulation increases podocyte cell number which is prevented following BIX02188 co-treatment^[3].

412.48

Solid

C₂₅H₂₄N₄O₂

334949-59-6

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 45 mg/mL(109.10 mM)

*"≥" means soluble, but saturation unknown.

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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
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• 1.

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

  Solubility: ≥ 1.67 mg/mL (4.05 mM); Clear solution

  此方案可获得 ≥ 1.67 mg/mL (4.05 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 16.7 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%corn oil

  Solubility: ≥ 1.67 mg/mL (4.05 mM); Clear solution

  此方案可获得 ≥ 1.67 mg/mL (4.05 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 16.7 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。