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Overview
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Background
GSK2334470 is a highly specific inhibitor of 3-phosphoinositide-dependent protein kinase 1(PDK1) with IC50 value of ~10nM [1].GSK2334470 prevents PDK1 from activating full-length Akt1or mutant Akt1 lacking the PH domain. It also inhibits phosphorylation of the PDKtide peptide substrate. GSK2334470 shows no significant inhibitory effect on 93 other protein kinases (including 13 AGC-kinases) and 15 lipid kinases. GSK2334470 markedly inhibits the IGF1-induced T-loop phosphorylation of SGK1, SGK2 and SGK3 overexpressed in HEK293 cells. GSK2334470 is also reported to suppress the activity of S6K1. It inhibits the phosphorylation of both hydrophobic motif and T-loop of S6K1. To Akt1, GSK2334470 exerts same effects on the phosphorylation of T-loop but has no significant inhibition of hydrophobic motif phosphorylation. In PDK1K465E/K465E knock-in ES cells, GSK2334470 is more potent to inhibit Akt activation than in PDK1+/+ ES cells. Moreover, the inhibition of Akt activation shows to recede in U87 glioblastoma cells lack PTEN expression [1].
[1] Najafov A, Sommer E, Axten J, et al. Characterization of GSK2334470, a novel and highly specific inhibitor of PDK1. Biochem. J, 2011, 433: 357-369.
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