Fragment-Based Drug Discovery of Potent Protein Kinase C Iota Inhibitors

Protein kinase C iota (PKC-i) is an atypical kinase implicated in the promotion of different cancer types. A biochemical screen of a fragment library has identified several hits from which an azaindole-based scaffold was chosen for optimization. Driven by a structure activity relationship and supported by molecular modeling, a weakly bound fragment was systematically grown into a potent and selective inhibitor against PKC-i.