Fig. 5.

Inhibition of APDS1 and APDS2 mutants by the potent PI3Kδ inhibitor idelalisib and model for activation of PI3Kδ and PI3Kα by APDS2 mutations in PIK3R1. (A) Inhibition of WT, APDS1, and APDS2 complexes of PI3Kδ by the potent PI3Kδ inhibitor idelalisib. Lipid kinase activity was normalized to kinase activity in the absence of inhibitors. IC₅₀ values were generated from triplicate independent inhibitor dilutions, and error is shown as SD. (B) Summary of the proposed mechanism for activation of the APDS2 PI3Kδ complex mapped on a schematic model with conformational changes and kinase activity data summarized.