AS-041164 is a potent and selective PI3Kγ inhibitor with IC50 value of 0.07 μM [1].
The phosphatidylinositol 3-kinases (PI3Ks) are a family of lipid and protein kinases regulating numerous biological processes, including cell growth, differentiation, survival, proliferation, migration and metabolism. PI3Kγ, a unique member of class IB, is activated exclusively by G-protein coupled receptor (GPCRs) and can specifically bind to adaptors unrelated to p85 proteins [2].
AS-041164 is a highly potent and selective PI3Kγinhibitor that inhibits PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ with IC50 values of 240 nM, 1.45 μM, 70 nM and 1.70 μM, respectively [1].
In mice, orally administration of AS-041164 dose-dependently decreased r-hRANTES-induced neutrophil recruitment with ED50 value of 27.35 mg/kg. AS-041164 (30 mg/kg p.o.) also significantly reduced r-hRANTES-induced AKT phosphorylation. In a carrageenan-induced inflammation rat model, AS041164 at the dose of 100 mg/kg p.o significantly reduced paw thickness induced by carrageenan [1].
References:
[1]. Ferrandi C, Ardissone V, Ferro P, et al. Phosphoinositide 3-kinase gamma inhibition plays a crucial role in early steps of inflammation by blocking neutrophil recruitment. J Pharmacol Exp Ther. 2007 Sep;322(3):923-30.
[2]. Hirsch E, Ciraolo E, Ghigo A, et al. Taming the PI3K team to hold inflammation and cancer at bay. Pharmacol Ther. 2008 May;118(2):192-205.