AS-604850 is a selective and ATP-competitive PI3Kγ inhibitor (IC50= 2.5 μM). It has over 30-fold selectivity for PI3Kδ and PI3Kβ, and 18-fold selectivity over PI3Kα.

PI3Kα:4.5 μM, PI3Kγ:0.25 μM, PI3Kγ:0.18 μM (Ki)

AS-604850 pretreatment abolished GCDC-induced phosphorylation of Akt by 50% and inhibited apoptosis by reducing GCDC/TCDC/TLC-induced caspase-3 cleavage in rat hepatocytes. In PI3KCG-/-monocytes and THP-1 (human monocytic cell line), AS-604850 inhibited the PKB phosphorylation activated by MCP-1, it also blocked the MCP-1-mediated chemotaxis in a concentration-dependent manner. In RAW264 mouse macrophages, C5a-mediated PKB phosphorylation was inhibited by AS-604850 [1][2].

In the thioglycollate-induced peritonitis model that induced multiple chemokines in vivo, oral administration of 10 mg/kg AS-604850 showed a 31% decrease in neutrophil recruitment [1].