Patrick T. Flaherty
David J Lapinsky
Jane E Cavanaugh
David A Johnson
The mitogen-activated protein kinases (MAPK) are a family of interrelated signal transduction kinases mediating intracellular responses to extracellular events. They are involved in mediating complex cellular events including, cell differentiation, cell proliferation, and cell death. Extracellular mitogens or the binding of other ligands to cell-surface receptors begin a signaling cascade that activates MEK resulting in phosphorylation of its corresponding and specific and parallel ERK (Extracellular signal-Regulated Kinase) substrate. The MEK5/ERK5 pathway is involved in cell survival, anti-apoptotic signaling, angiogenesis, and cell motility. It is significantly up-regulated in specific tumor types including breast and prostate cancers. A novel series of compounds utilizing the diphenylamine scaffold was designed and synthesized based on a homology model of MEK5 using the X-ray crystal structure of MEK1 (PDB ID: 3EQC) as a template. The compounds were tested for their MEK12, and MEK5 inhibition in a cell based assay.
Chakrabarty, S. (2014). Design, Synthesis and Evaluation of Diphenylamines as MEK5 Inhibitors (Master's thesis, Duquesne University). Retrieved from https://dsc.duq.edu/etd/388