Identification of potent inhibitors of the sortilin-progranulin interaction. Issue 17 (1st September 2020) - Stachel, Shawn J.
Graphical abstract: Abstract: High-throughput screening methods have been used to identify two novel series of inhibitors that disrupt progranulin binding to sortilin. Exploration of structure-activity relationships (SAR) resulted in compounds with sufficient potency and physicochemical properties to enable co-crystallization with sortilin. These co-crystal structures supported observed SAR trends and provided guidance for additional avenues for designing compounds with additional interactions within the binding site.