Phosphatidylinositol 3-kinase (PI3K) catalyzes the phosphorylation of PI at the three position of the inositol ring to produce the second messengers PtdIns-(3,4)-P2 and PtdIns-(3,4,5)-P3. PI3Kγ is a class 1B PI3K that is composed of a p110 catalytic subunit and a p101 or p84 regulatory subunit, whereas PI3Kα, β, and δ are class 1A enzymes composed of p110 and p85 subunits. AS-604850 is a selective, ATP-competitive inhibitor of PI3Kγ with IC50 values of 0.25, >20, >20, and 4.5 μM for the human recombinant γ, δ, β, and α isoforms, respectively. AS-604850 inhibited MCP-1-mediated monocyte chemotaxis with an IC50 value of 21 μM and reduced RANTES-induced peritoneal neutrophil recruitment in a murine model of leukocyte chemotaxis with an ED50 value of 42.4 mg/kg.
