AZD 6482

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.{8039,12235,13740} PI3K?, ?, and ? are class 1A enzymes composed of p110 and p85 subunits, whereas PI3K? is a class 1B PI3K composed of a p110 catalytic subunit and a p101 or p84 regulatory subunit.{14518} AZD 6482 is a PI3K inhibitor that targets the ? isoform more potently than PI3K?, PI3K?, or PI3K? (IC50s = 0.69, 13.6, 47.8, and 136 nM, respectively).{29907} It displays 80-fold selectivity for PI3K? over PI3k-C2 and DNA-PK and more than 1,000-fold over other PI3K-related kinases.{29907} AZD 6482 blocks Akt signaling and tumor growth in a large number of cancer cell lines, including those that are dependent on PI3K? activation or PTEN loss.{29907,29910,29908} AZD 6482 (20 mg/kg, i.p.) suppresses the growth of PTEN-deficient xenograft tumors in mice.{29907} It also produces an anti-thrombotic effect in dogs without an increase in bleeding time or blood loss.{29909}