PIK-294

PIK-294 is a potent p110δ-selective inhibitor with an IC50 of 10 nM.

Research Areas >> Cancer

p110δ:10 nM (IC50)

p110γ:160 nM (IC50)

p110β:490 nM (IC50)

p110α:10 μM (IC50)

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].

Neutrophils at a concentration of 6×106 cells/mL are pre-treated with 1 μM and 10 μM of the PIK-294 for 30 mins prior to the addition of CXCL8 (100 ng/mL) or 0.5 ng/mL GM-CSF. Then a non-gradient or gradient gel assay depending on the type of migration is performed. The gels are then constructed and the migration studied[2].

[1]. Knight ZA, et al. A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell. 2006 May 19;125(4):733-47.

[2]. Martin KJ, et al. The role of phosphoinositide 3-kinases in neutrophil migration in 3D collagen gels. PLoS One. 2015 Feb 6;10(2):e0116250.

3-Methyladenine | LY294002 | Wortmannin | Alpelisib (BYL719) | BKM120 | Eganelisib(IPI-549) | BAY 80-6946 (Copanlisib) | Idelalisib (CAL-101) | Dactolisib (BEZ235) | Quercetin | SAR-405 | GDC-0941 | 740 Y-P | LY3023414 | 1,3-Dicaffeoylquinic acid