MEK inhibitor CI-1040 but not Raf inhibitor BAY 43-9006 reduces lung adenomas in vivo. (A) MEK activity was completely inhibited in vitro by BAY 43-9006 and CI-1040 as determined by ERK activation enzyme-linked immunosorbent assay. IC50 values for BAY 43-9006 and CI-1040 were 16 nM and 12 nM respectively. (B, C) The amount of P-ERK and the number of P-ERK positive cells were reduced in vivo by treatment with CI-1040 but not with BAY 43-9006. (D, E, F) Treatment with CI-1040 but not with BAY 43-9006 reduced adenomas and improved lung structure after 21d (hematoxylin and eosin staining; scale bars = 60 μm). Lung adenomas as well as the overall lung morphology was indistinguishable in placebo treated and untreated animals (data not shown).