Pharmacological Inhibitors of Nedd4 ubiquitin ligase as anticancer therapeutics

IGF-1 and Insulin cell growth pathways activate downstream PI3K/Akt cell signaling and are one of the most frequently activated cell growth pathways in human cancers. Nedd4-1 is a critical HECT E3 ubiquitin ligase, which is required for IGF-1/Insulin cell signaling, therefore the inhibition of Nedd4-1 with small molecule inhibitors is a promising strategy to treat human cancers. The proposed project addresses this need by discovering first-in-class covalent inhibitors of Nedd4-1 enzyme, which inhibit its processivity.