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 (IC50 12 nM) and its favorable kinase selectivity profile [2, 3]. 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.
bay43-9006, mek-1, erk-1, raf kinase inhibitor, raf/mek/erk signaling
Bayer Research Center, Institute for Preclinical Drug Development, Bayer Corporation, Pharmaceutical Division, 400 Morgan Lane, West Haven, CT 06516, USA