A-674563 hydrochloride

Three related forms of the kinase Akt (1, 2, 3, also known as protein kinase B isoforms PKBα, β, γ) modulate cell proliferation, metabolism, and survival, as well as angiogenesis. A-674563 is an orally available, ATP-competitive, and reversible inhibitor of Akt (K_i = 11 nM for Akt1).¹ It shows inhibitory activity against PKA and Cdk2 with IC₅₀ values of 16 and 46 nM, respectively, but is 10- to >1,800-fold selective for Akt1 versus additional kinases in the CMGC, CAMK, and TK families.¹ A-674563 reduces phosphorylation of Akt downstream targets in cells and slows proliferation of tumor cells in vitro with an EC₅₀ value of 0.4 ?M.¹ In vivo, 40 mg/kg/day A-674563 in combination with 15 mg/kg/day paclitaxel was shown to decrease tumor growth in a PC-3 prostate cancer mouse xenograft model.¹

1.Luo, Y., Shoemaker, A.R., Liu, X., et al.Potent and selective inhibitors of Akt kinases slow the progress of tumors in vivoMol. Cancer Ther.4(6)977-968(2005)