Array BioPharma (ARRY)

About MEK

MEK is a key protein kinase in the RAS/RAF/MEK/ERK pathway, which mediates production of key proinflammatory cytokines, including TNFa, IL-1b and IL-6, as well as cellular proliferation and survival. It also has a role in pathogenic bone remodeling through direct effects on osteoclasts, the cells responsible for bone resorption.  MEK inhibition therefore has the potential to be a novel and safe approach to treating chronic, progressive inflammatory diseases because of its observed anti-inflammatory and bone anti-resorptive effects. In addition, MEK is frequently activated in cancer, in particular in tumors that have mutations in the RAS and RAF oncogenes. Preclinical data show that MEK inhibitors are additive or synergistic in combination with other agents. In particular, the PI-3K/AKT/mTOR pathway interacts with the RAS/RAF/MEK/ERK pathway in response to growth factor signaling. Simultaneous inhibition of both these pathways has significantly greater preclinical anti-tumor activity compared to inhibition of either pathway alone. Because these pathways are commonly activated in many tumors, we believe that dual MEK and PI3K/AKT/mTOR inhibition could have broad anti-tumor activity.

About MEK

MEK is a key protein kinase in the RAS/RAF/MEK/ERK pathway, which signals for cancer cell proliferation and survival.  MEK is frequently activated in cancer, in particular in tumors that have mutations in the RAS and RAF oncogenes.  MEK also regulates the biosynthesis of the inflammatory cytokines TNF, IL-6 and IL-1, which can act as growth and survival factors in cancer.  Preclinical data show that MEK inhibitors are additive or synergistic in combination with other agents.  In particular, the PI-3K/AKT/mTOR pathway interacts with the RAS/RAF/MEK/ERK pathway in response to growth factor signaling.  Simultaneous inhibition of both these pathways has significantly greater preclinical anti-tumor activity compared to inhibition of either pathway alone.  Because these pathways are commonly activated in many tumors, we believe that dual MEK and PI3K/AKT/mTOR inhibition could have broad anti-tumor activity.

About MEK:

MEK is a protein kinase that regulates both the biosynthesis of and response to a number of growth factors that drive uncontrolled inflammation associated with many human diseases. Our scientists have discovered multiple series of MEK inhibitors that selectively interfere with these critical disease processes. Our first MEK inhibitor, ARRY-142886, was licensed to AstraZeneca AB for cancer and is currently in clinical development.  Array’s new proprietary molecule, ARRY-438162, is a potent and selective inhibitor in enzyme and cellular systems, and is well-tolerated and efficacious in various preclinical models of human diseases driven by inflammatory growth factors like TNFα, IL-1 and IL-6.  These results, together with our extensive experience with the safety profile of MEK inhibitors, lead us to believe that MEK inhibition will be useful in treating acute and chronic inflammatory diseases, including rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD).