Figure 6.

Structure based design leads to novel, potent GSK3α inhibitors (A,B) results from p-Thr231 cell-based assay illustrate improvements in potency of both compound 2 and compound 3 when compared to previously profiled inhibitors. Each data point represents the mean ± SEM from four biological replicates within a single run of the assay. (C,D) Nanobret assay was used to further verify the potency and selectivity of the novel inhibitors compound 2 and compound 3. Each data point represents the mean ± SEM from four biological replicates within a single run of the assay. (E,F) Both compound 2 and compound 3 show significantly longer residence times for GSK3α in comparison to the parent molecule compound 1. These compounds did not differ in their residence times for GSK3β. Each data point represents the mean ± SEM from eight biological replicates within single run of the assay.