1198802-79-7Relevant articles and documents
From PIM1 to PI3Kδ via GSK3β: Target Hopping through the Kinome
Henley, Zo? A.,Bax, Benjamin D.,Inglesby, Laura M.,Champigny, Aurélie,Gaines, Simon,Faulder, Paul,Le, Joelle,Thomas, Daniel A.,Washio, Yoshiaki,Baldwin, Ian R.
supporting information, p. 1093 - 1098 (2017/10/18)
Selective inhibitors of phosphoinositide 3-kinase delta are of interest for the treatment of inflammatory diseases. Initial optimization of a 3-substituted indazole hit compound targeting the kinase PIM1 focused on improving selectivity over GSK3β through consideration of differences in the ATP binding pockets. Continued kinase cross-screening showed PI3Kδ activity in a series of 4,6-disubstituted indazole compounds, and subsequent structure-activity relationship exploration led to the discovery of an indole-containing lead compound as a potent PI3Kδ inhibitor with selectivity over the other PI3K isoforms.