Xiaoshuai Cheng

A Kinetic Originof Vps34-IN-3 Selectivityfor VPS34 over PI3Kα Revealed by Supervised Molecular Dynamicsand Potential of Mean Force Analysis

Abstract The rational design of selective kinase inhibitors is hampered by the conserved ATP-binding pockets. Vps34-IN-3, a potent VPS34 inhibitor developed by Genentech, Inc., showed ∼95-fold selectivity over the closely related PI3Kα, yet the atomic-level mechanism underlying t...