Design, Synthesis and Biological Evaluation of Lapatinib Derivatives as HER1/HER2 Inhibitors

Five Lapatinib derivatives were designed by structurally modifying the side chain as well as the aniline substituent. The ELISA assay showed that the derivatives retained or even improved the inhibitory activity of Lapatinib against HER1/HER2. In vitro cytotoxicity assay revealed that the derivatives significantly inhibited the proliferation of the HER1/HER2-overexpressing cancer cells. Furthermore, molecular modeling study suggested that the derivative could effectively enter the ATP binding pocket of HER1 and interact with the corresponding residues in a manner similar to Lapatinib.