Structural factors contributing to the Abl/Lyn dual inhibitory activity of 3-substituted benzamide derivatives
| Autor: | Hiroki Hayase, Shinsaku Itou, Tatsuya Horio, Tomohiro Hamasaki, Toshihiko Inoue, Tomoko Niwa, Tetsuo Asaki, Haruna Naito, Tatsushi Wakayama |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Tertiary amine
Clinical Biochemistry Molecular Conformation Pharmaceutical Science Biochemistry Structure-Activity Relationship chemistry.chemical_compound LYN hemic and lymphatic diseases Drug Discovery Humans Enzyme Inhibitors Binding site Proto-Oncogene Proteins c-abl Benzamide Molecular Biology ABL Kinase Chemistry Organic Chemistry Pyrimidines src-Family Kinases Benzamides Molecular Medicine Signal transduction Tyrosine kinase |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 17:2712-2717 |
| ISSN: | 0960-894X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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