Mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) pathway, also known as MEK pathway, is reported to be associated with the cell proliferation, differentiation, migration, senescence and apoptosis[3]. BIX-02188 is a potent MEK5-selective inhibitor with an IC50 of 4.3 nM. BIX02188 inhibits ERK5 catalytic activity, with an IC50 of 810 nM[4]. In activated HeLa cells, BIX-02188 blocks phosphorylation of ERK5, without affecting phosphorylation of ERK1/2, c-Jun amino terminal kinase (JNK) and p38 MAP kinases. Phosphorylated BMK1 (ERK5) is inhibited by BIX-02188 in a dose-dependent manner, with an IC50 of 0.8±1.0 μM, and maximal inhibition at concentrations >3 μM, which confirms the selectivity of BIX-02188 for MEK5-induced BMK1 phosphorylation[5]. When podocytes are pre-incubated in the absence or presence of BIX-02188 (10 μM) for 60 min, Inhibition of Erk5 activation with BIX-02188 incubation reduces podocyte cell number[6].
BIX02188 细胞实验
Cell Line
Concentration
Treated Time
Description
References
DRG neurons
30 μM
12 h
BIX02188 was able to attenuate NGF-induced BDNF up-regulation in the DRG soma
Exp Neurol. 2012 Dec;238(2):209-17
PC12 cells
30 μM
30 min
BIX02188 selectively inhibited ERK5 phosphorylation without affecting ERK1/2 phosphorylation.
J Biol Chem. 2009 Aug 28;284(35):23564-73.
MC3T3-E1 cells
5μM
7 days
To evaluate the role of the ERK5 signaling pathway in osteogenesis promoted by silver ion-loaded titanium dioxide nanotube arrays. Results showed that inhibition of the ERK5 signaling pathway significantly suppressed the osteogenic capabilities of MC3T3-E1 cells.
Int J Nanomedicine. 2025 Mar 24;20:3749-3764
human podocytes
10μM
60 min pre-incubation
Inhibition of Erk5 phosphorylation, preventing TGFβ1-induced podocyte proliferation and phenotype changes
Front Pharmacol. 2014 Apr 21;5:71
BIX02188 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Wistar rats
Spinal cord injury model
Intrathecal injection
1 mg/mL, 10 mL each time
Injected at 1, 6, and 12 hours post-surgery, lasting for 24 hours
To evaluate the role of ERK5 signaling pathway in spinal cord injury. Results showed that BIX02188 inhibited the ERK5 signaling pathway, reduced the degree of spinal cord tissue injury, neutrophil infiltration and proinflammatory cytokine expression, and suppressed NF-κB activation and apoptosis.
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