PI3Kγ
0.25 μM (IC 50 )
0.18 μM (Ki)
PI3Kα
4.5 μM (IC 50 )
AS-604850 inhibits C5a-mediated PKB phosphorylation with an IC 50 of 10 μM in RAW264 mouse macrophages. AS-604850 blocks PKB phosphorylation induced by MCP-1 and has little or no effect after stimulation with CSF-1 in in primary monocytes from Pik3cg +/+ or Pik3cg –/– mice. AS-604850 (0-30 μM; 15 minutes; primary monocytes from Pik3cg +/+ mice) treatment inhibits MCP-1-mediated phosphorylation of PKB and its downstream substrates GSK3α andβ in a concentration-dependent manner. MCP-1-induced phosphorylation of p44/42 ERK (ERK1/2) MAPKs is also reduced, in a concentration dependent manner in primary monocytes from Pik3cg +/+ mice.
Western Blot Analysis
AS-604850 (10-100 mg/kg; oral administration; for 4.5 or 4.25 hours; Balb/C or C3H mice) treatment reduces RANTES-induced peritoneal neutrophil recruitment with an ED 50 value of 42.4 mg/kg. In the thioglycollate-induced peritonitis model, oral administration of 10 mg/kg AS-604850 results in a 31% reduction of neutrophil recruitment.