Discovery of a novel series of Notch-sparing γ-secretase inhibitors

Using a cell-based assay, we have identified a new series of Notch-sparing γ-secretase inhibitors from HTS screening leads 2a and 2e. Lead optimization studies led to the discovery of analog 8e with improved γ-secretase inhibitory potency and Notch-sparing selectivity.

Lead optimization studies of Notch-sparing GSI 2a led to the discovery of analog 8e with improved γ-secretase inhibitory potency and Notch-sparing selectivity.Figure optionsDownload as PowerPoint slide