Identification of benzimidazole-based inhibitors of the mitogen activated kinase-5 signaling pathway

Identification of novel benzimidazole inhibitors of MEK5 mediated phosphorylation of ERK5 is presented and early effects of structure on activity are presented. The MEK-signaling pathways are complex but critical signaling cascades that correlate an extracellular signaling event with internal cell processes. To date at least seven MEK isozymes have been identified. MEK5, in particular, is upregulated in multiple forms of tumors. Analysis of the EGF-induced MEK5 signaling cascade in cultured HEK cells has identified compounds that can inhibit MEK5 phosphorylation of ERK5; observed biological activity is dependent on chemical variation.