Author/Authors :
Dan Berger، نويسنده , , Minu Dutia، نويسنده , , Dennis Powell، نويسنده , , Biqi Wu، نويسنده , , Allan Wissner، نويسنده , , Diane H. Boschelli، نويسنده , , M. Brawner Floyd، نويسنده , , Nan Zhang، نويسنده , , Nancy Torres، نويسنده , , Jeremy Levin، نويسنده , , Xuemei Du، نويسنده , , Donald Wojciechowicz، نويسنده , , Carolyn Discafani، نويسنده , , Constance Kohler، نويسنده , , Steven C. Kim، نويسنده , , Larry R. Feldberg، نويسنده , , Karen Collins، نويسنده , , Robert Mallon، نويسنده ,
Abstract :
4-[3-Chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)]anilino-6,7-diethoxy-3-quinolinecarbonitrile (3) was identified as a MEK1 kinase inhibitor with exceptional activity against LoVo cells. The structure–activity relationships of the C-4 aniline substituents were explored, and water-solubilizing groups were added at the C-7 position to improve physical properties. Secondary cellular assays revealed that a compound possessing the appropriate aniline substituents inhibited MEK1 as well as MAPK phosphorylation, thereby acting as a dual inhibitor of the Ras-MAPK signaling cascade.
