The mitogen-activated protein kinase pathway is thought to be essential in
cellular growth and differentiation. Here we report the discovery of a high
ly potent and selective inhibitor of the upstream kinase MEK that is orally
active. Tumor growth was inhibited as much as 80% in mice with colon carci
nomas of both mouse and human origin after treatment with this inhibitor. E
fficacy was achieved with a wide range of doses with no signs of toxicity,
and correlated with a reduction in the levels of activated mitogen-activate
d protein kinase in excised tumors. These data indicate that MEK inhibitors
represent a promising, noncytotoxic approach to the clinical management of
colon cancer.