PIK-294

PIK-294 is a potent p110δ-selective inhibitor with an IC₅₀ of 10 nM. IC50 & Target: IC50: 10 nM (p110δ), 0.16 μM (p110γ), 0.49 μM (p110β), 10 μM (p110α)^[1] In Vitro: Analysis of the specific Class I PI3 Kinase catalytic isoforms p110α (IC₅₀=10 μM), p110β (IC₅₀=0.49 μM), p110δ (IC₅₀=0.01 μM) and p110γ (IC₅₀=0.16 μM) using the inhibitor PIK-294 indicates differential roles in CXCL8-induced neutrophil migration. PIK-294 inhibits both chemokinetic and chemotactic CXCL8-induced migration^[1]. When cells are pre-treated with the PI3Kδ selective inhibitor PIK-294, CXCL8-induced migration in the non-gradient and the gradient assay is significantly inhibited. PIK-294 is used at two concentrations 1 μM and 10 μM. Pre-treatment with 1 μM inhibits migration to a greater extent in the non-gradient assay than in the gradient assay. Pre-treatment with 10 μM inhibits migration to a significantly greater extent than the lower dose in both assays. Prior to stimulation with CXCL8, pre-treatment of the cells with the PI3K inhibitors, Wortmannin (50 nM), PIK-294 (10 μM) and AS-605240 (10 μM) for 2 minutes, cause a reduction in the phosphorylation of Akt. Pre-treatment of cells prior to stimulation with GM-CSF and the DMSO control with the PI3K inhibitors Wortmannin (50 nM), PIK-294 (10 μM) and AS-605240 (10 μM) for 2 minutes, reduce the phosphorylation of Akt (p<0.05 for inhibition of PI3Kδ)^[2].