POTENT SMALL MOLECULE INHIBITORS OF AUTOPHAGY, AND METHODS OF USE THEREOF

摘要

Certain aspects of the invention relate to small molecule autophagy inhibitors, and their use for treatment and prevention of cancers and acute pancreatitis. Medicinal chemistry studies led to small molecular autophagy inhibitors with improved potency and selectivity. Vps34 (vacuolar protein sorting 34), a type III Ptdins3 kinase (phosphatidylinositol 3-kinase ), was first identified as a regulator of vacuolar hydrolase sorting in yeast (Herman and Emr, 1990). Vps34 specifically phosphorylates the D-3 position on the inositol ring of hos hatid linositol Ptdins to roduce Ptdins3P.