A-674563 is a potent and selective PKB/Akt inhibitor with an IC50 of 14 nM. It binds to ATP-binding site of Akt and reduces the phosphorylation of Akt's downstream targets (GSK3α/β, FOXO3, TSC2, mTOR and S6, etc.). A-674563 also inhibits activity of PKA and CDK2 with IC50 of 16 and 46 nM, respectively. A-674563 inhibits proliferation of tumor cells with IC50 of 0.4 µM¹.

In STS cells, A-674563 induces Akt pathway blockade that decreases downstream target phosphorylation, and induces G2 cell cycle arrest and apoptosis. In vivo, A-674563 reduces STS xenograft growth². When given in combination, A-674563 enhanced the efficacy of paclitaxel in a PC-3 xenograft model¹.