title: Structural factors contributing to the Abl/Lyn dual inhibitory activity of 3-substituted benzamide derivatives.
abstract: 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.
authors: Research Laboratories, Nippon Shinyaku Co. Ltd., 3-14-1 Sakura, Tsukuba, Ibaraki 305-0003, Japan.
authors: Tatsuya
authors: T
authors: Horio
authors: Tomohiro
authors: T
authors: Hamasaki
authors: Toshihiko
authors: T
authors: Inoue
authors: Tatsushi
authors: T
authors: Wakayama
authors: Shinsaku
authors: S
authors: Itou
authors: Haruna
authors: H
authors: Naito
authors: Tetsuo
authors: T
authors: Asaki
authors: Hiroki
authors: H
authors: Hayase
authors: Tomoko
authors: T
authors: Niwa
mesh_terms: D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008968:Molecular Conformation; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D011743:Pyrimidines; C037689:benzamide; D016315:Proto-Oncogene Proteins c-abl; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; C506918:bafetinib