The phosphatidylinositol 3-kinases (PI3Ks) are lipid and protein kinases involved in diverse biological processes, including cell growth, migration, and metabolism. AS-041164 is a potent inhibitor of PI3K with selectivity for the class IB isoform PI3Kγ (IC50 = 70 nM), compared to PI3Kα (IC50 = 240 nM), PI3Kβ (IC50 = 1.45 μM), and PI3Kδ (IC50 =1.70 μM). When tested at 1.0 μM, it shows little or no activity against 38 other common kinases. When given orally to mice, AS-041164 shows a pharmacokinetic profile that is similar to the general PI3K inhibitor LY294002 but is three times more potent (ED50 = 27.4 mg/kg for AS-041164 versus 81.6 mg/kg for LY294002) in blocking neutrophil recruitment induced by RANTES.
AS-041164 is a potent, selective and orally active PI3Kγ isoform inhibitor with an IC50 of 70 nM. AS-041164 shows less activity against PI3Kα, PI3Kβ, and PI3Kδ (IC50s of 240 nM, 1.45 μM, and 1.70 μM, respectively). AS-041164 has anti-inflammatory effects[1].
AS-041164 (10-100 mg/kg; oral administration; once) treatment results in the reduction of inflammatory swelling in the model of carrageenan-induced paw edema[1].
AS-041164 (3-100 mg/kg p.o.) treatment dose-dependently decreases r-h regulated on activation normal T cell expressed and secreted (RANTES)-induced neutrophil recruitment in mice. The ED50 value for AS-041164 is 27.35 mg/kg. AS-041164 blocks RANTES-induced chemotaxis and reduces the level of AKT phosphorylation[1].
| Animal Model: | Male Wistar rats (100-150 g) injected with carrageenan[1] |
| Dosage: | 10 mg/kg, 30 mg/kg, 100 mg/kg |
| Administration: | Oral administration; once |
| Result: | Induced a significant reduction of paw thickness. |
PI3Kγ: 70 nM (IC50); PI3Kα: 240 nM (IC50); PI3Kβ: 1.4 μM (IC50); PI3Kδ: 1.7 μM (IC50)
[1] CHIARA FERRANDI. Phosphoinositide 3-kinase gamma inhibition plays a crucial role in early steps of inflammation by blocking neutrophil recruitment.[J]. Journal of Pharmacology and Experimental Therapeutics, 2007, 322 3: 923-930. DOI:
10.1124/jpet.107.123026
