BIX-02188 is a selective inhibitor of MEK5 with IC50 of 4.3 nM, also inhibits ERK5 catalytic activity with IC50 of 810 nM, and does not inhibit closely related kinases MEK1, MEK2, ERK2, and JNK2.
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].
搜索
