Discovery of Potent, Efficient, and Selective Inhibitors of Phosphoinositide 3-Kinase δ through a Deconstruction and Regrowth Approach.

A deconstruction of previously reported phosphoinositide 3-kinase δ (PI3Kδ) inhibitors and subsequent regrowth led to the identification of a privileged fragment for PI3Kδ, which was exploited to deliver a potent, efficient, and selective lead series with a novel binding mode observed in the PI3Kδ crystal structure.