AS 604850

Description

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.

Uses

AS-604850 is a selective and ATP-competitive phosphoinositide 3-kinase gamma (PI3Kγ) inhibitor.

in vivo

IC 50

PI3Kγ: 0.25 μM (IC₅₀); PI3Kγ: 0.18 μM (Ki); PI3Kα: 4.5 μM (IC₅₀)

References

1. camps m, rückle t, ji h et al. blockade of pi3k-gamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. nat med. 2005 sep;11(9):936-43.2. hohenester s, gates a, wimmer r et al. phosphatidylinositol-3-kinase p110γ contributes to bile salt-induced apoptosis in primary rat hepatocytes and human hepatoma cells. j hepatol. 2010 nov;53(5):918-26.