The drug design and discovery efforts described in the previous section led to the development of a novel, small molecule Raf-1 kinase inhibitor, BAY 43-9006, which belongs to a class that can be broadly described as bis-aryl ureas (Figure 1). BAY 43-9006 was identified during a large medicinal chemistry optimization program, and this compound was selected for further pharmacological characterization based on its potent inhibition of Raf-1 (IC(50) 12 nM) and its favorable kinase selectivity profile. In vitro and in vivo experiments were designed to demonstrate effective blockade of the Raf/MEK/ERK signaling pathway in tumor cells and for anti tumor efficacy in human xenograft models.