PI3-Kinase α Inhibitor 2

Phosphatidylinositol 3-kinase (PI3K) catalyzes the phosphorylation of the 3' hydroxyl position of PIs to produce the second messengers PtdIns-(3,4)-P2 and PtdIns-(3,4,5)-P3. PI3Kα, β, and δ are class 1A enzymes composed of p110 and p85 subunits, whereas PI3Kγ is a class 1B PI3K composed of a p110 catalytic subunit and a p101 or p84 regulatory subunit. PI3Kα inhibitor 2 is a selective inhibitor of PI3Kα with IC50 values of 2, 16, 660, and 220 nM for the α, β, γ, and 2Cβ isoforms, respectively. It inhibits PKA, KDR, PKCα, and cyclin E/Cdk2 significantly less effectively (IC50 = 91, 3.4, 466, and 28 µM, respectively). PI3Kα inhibitor 2 inhibits A375 melanoma cell proliferation with an IC50 value of 580 nM.