PIK-75 (PIK-75 hydrochloride) is a potent, isoform-selective p110α inhibitor with IC50 of 0.3 nM, displays >100-fold selectivity over p110β, p110δ and PI3K C2b.
PIK-75 blocks the phosphorylation of PKB induced by insulin on both Ser473 and Thr308 in CHO-IR cell (IC50=78 nM), inhibits PI3K activation associated with dramatic suppression of downstream signaling events, including AKT phosphorylation, IKK activation, and NF-kappaB transcription.
PIK-75 potently and dose dependently inhibits in vitro and in vivo production of TNF-alpha and IL-6, diminishes the induced expression of human endothelial cell adhesion molecules (E-selectin, ICAM-1, and VCAM-1), and blocks human monocyte-endothelial cell adhesion.
PIK-75 exhibits significant anti-tumor effectiveness in vivo.
