Figure 1.

(a) Biochemical potency and selectivity values of PI3Kγ-selective inhibitors, as reported in the literature (see Supporting Information for a comparison of literature and in-house assay protocols). Inhibition determined using the ADP-Glo assay (Promega). Reported ATP K_m = 29 ± 3.7 μM.^34aAssay conditions: 3 mM ATP, 500 μM dioctanoyl-phosphatidylinositol-4,5-bisphosphate (diC₈PIP₂) as substrate, and 40 nM PI3Kγ. ^bAssay conditions: 1 μM ATP, 10 μM PIP₂, and 30 nM PI3Kγ. ^cAssay conditions: 20 μM ATP, 80 μM diC₈PIP₂, and 1.2 nM PI3Kγ. (b) Schematic of typical inhibitor binding modes within PI3Kγ, exemplified by 2.²⁵