BIX02189

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

BIX02189 是 MEK5 催化活性的有效选择性抑制剂，IC50 为 1.5 nM，还抑制 ERK5 催化活性 (IC50=59 nM)。

BIX02189 is a potent, selective inhibitor of MEK5 catalytic activity with IC50 of 1.5 nM, also inhibits ERK5 catalytic activity (IC50=59 nM), does not inhibits closely related kinases MEK1, MEK2, ERK2, and JNK2; ; blocks phosphorylation of ERK5, without affecting phosphorylation of ERK1/2 in sorbitol-stimulated HeLa cells, also inhibits transcriptional activation of MEF2C, a downstream substrate of the MEK5/ERK5 signaling cascade; blocks ERK5 signaling and suppresses NGF-induced neurite outgrowth in PC12 cells.

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.

BIX 02189 | BIX-02189

MAPK/ERK Signaling

MEK

MEK

Cancer

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1265916-41-3

440.5368

C27H28N4O2

>98% (HPLC)

DMSO: ≥ 49.4 mg/mL

CN(C)CC1=CC(=CC=C1)N=C(C2=CC=CC=C2)C3=C(NC4=C3C=CC(=C4)C(=O)N(C)C)O

1H-Indole-6-carboxamide, 3-[[[3-[(dimethylamino)methyl]phenyl]amino]phenylmethylene]-2,3-dihydro-N,N-dimethyl-2-oxo-, (3Z)-

(-20℃)

With Ice Pack

≥ 2 years