AZD6428 is a potent, selective and ATP-competitive PI3Kβ inhibitor. IC50 are 0.69, 13.6, 47.8 and 136 nM for PI 3-Kβ, PI 3-Kδ, PI 3-Kγ and PI 3-Kα, respectively.
PI3K (phosphatidylinositol-4,5-bisphosphate 3-kinase) is a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. It plays a key role in PI3K/Akt/mTOR pathway.
In vitro, AZD6482 inhibited insulin-activated uptake of human adpocyte glucose (IC50=4.4 μm). A full anti-thrombotic response with no increased bleeding or blood loss was observed in dog treated with AZD6482 in vivo. It also showed good tolerance in a three-hour AZD6482 infusion in healthy volunteers. There was an approx.10-20% rise at 5.3 μm (highest plasma concentration) according to the homeostasis model analysis index. [1]
Reference:
[1].Nylander S, Kull B, Björkman JA et al. Human target validation of phosphoinositide 3-kinase (PI3K)β: effects on platelets and insulin sensitivity, using AZD6482 a novel PI3Kβ inhibitor. J Thromb Haemost. 2012 Oct;10(10):2127-36.