Structural factors contributing to the Abl/Lyn dual inhibitory activity of 3-substituted benzamide derivatives.

Tatsuya Horio, Tomohiro Hamasaki, Toshihiko Inoue, Tatsushi Wakayama, Shinsaku Itou, Haruna Naito, Tetsuo Asaki, Hiroki Hayase, Tomoko Niwa

Research Laboratories, Nippon Shinyaku Co. Ltd., 3-14-1 Sakura, Tsukuba, Ibaraki 305-0003, Japan.

Bioorganic & medicinal chemistry letters 2007 May 15

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To investigate why 3-substituted benzamide derivatives show dual inhibition of Abl and Lyn protein tyrosine kinases, we determined their inhibitory activities against Abl and Lyn, carried out molecular modeling, and conducted a structure-activity relationship study with the aid of a newly determined X-ray structure of the Abl/Lyn dual inhibitor INNO-406 (formerly known as NS-187) bound to human Abl. We found that this series of compounds interacted with both kinases in very similar ways, so that they can inhibit both kinases effectively.

Citation

Tatsuya Horio, Tomohiro Hamasaki, Toshihiko Inoue, Tatsushi Wakayama, Shinsaku Itou, Haruna Naito, Tetsuo Asaki, Hiroki Hayase, Tomoko Niwa. Structural factors contributing to the Abl/Lyn dual inhibitory activity of 3-substituted benzamide derivatives. Bioorganic & medicinal chemistry letters. 2007 May 15;17(10):2712-7