Assessing the Target Differentiation Potential of Imidazole-Based Protein Kinase Inhibitors

作者:Dimova Dilyana; Iyer Preeti; Vogt Martin; Totzke Frank; Kubbutat Michael H G; Schaechtele Christoph; Laufer Stefan*; Bajorath Juergen
来源:Journal of Medicinal Chemistry, 2012, 55(24): 11067-11071.
DOI:10.1021/jm3014508

摘要

A library of 484 imidazole-based candidate inhibitors was tested against 24 protein kinases. The resulting activity data have been systematically analyzed to search for compounds that effectively differentiate between kinases. Six imidazole derivatives with high kinase differentiation potential were identified. Nearest neighbor analysis revealed the presence of close analogues with varying differentiation potential. Small structural modifications of active compounds were found to shift their inhibitory profiles toward kinases with different functions.

  • 出版日期2012-12-27