REVIEW The compound (Akt-I-1) inhibits only Akt1 (IC50 4.6 μM) and does not inhibit AKT2, or AKT3. The compound is a reversible inhibitor, and exhibits a linear mixed-type inhibition against ATP and peptide substrate. In addition to inhibiting kinase activity of AKT1 isoform, AKT-I-1 blocked the phosphorylation and activation of AKT1 by PDK1 (phosphoinositide-dependent kinase 1). The inhibitor was found to be cell-active and to block phosphorylation of Akt at Thr308 and Ser473, reduce the levels of active Akt in cells, block the phosphorylation of known Akt substrates and promote TRAIL (tumour-necrosis-factor-related apoptosis-inducing ligand)-induced apoptosis in LNCap prostate cancer cells.
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