Discovery of a novel Raf kinase inhibitor

We discuss the biology of Ras signal transduction and the epidemiology of r as mutations in association with disease as a background for the developmen t of a Raf kinase inhibitor, BAY 43-9006. Knowledge of Ras effector pathway s has permitted genetic validation of numerous targets involved in the Ras signaling cascade. A key Ras effector pathway involves the kinase cascade R AF/MEK/ERK (MEK: MAP/ERK kinase; ERK: extracellular signal related kinase). Indeed, we present studies of cell lines stably expressing mutant MEK cons tructs, which point to Raf kinase as a target for therapeutics with selecti ve anti-tumor activity. Finally, a small molecule drug discovery program ba sed on inhibition of Raf kinase activity is outlined and the initial pre-cl inical development process of the Raf kinase inhibitor BAY 43-9006 is discu ssed.