Table 3.
Activator | Activation potency | Mode of activation | Notes |
---|---|---|---|
Celecoxib | IC50 = 3.5 μM | Inhibits PDK phosphorylation of Akt | COX-2 inhibitor [100]. |
Staurosporine | IC50 = 0.22 μM | Inhibits PDK phosphorylation of Akt | General kinase inhibitor (including PKA/PKC) [101, 103, 104]. |
Trichostatin A | Unknown | Induces Akt dephosphorylation | HDAC inhibitor acts through PP1 [105]. |
Curcumin | Unknown | Akt dephosphorylation | Direct target not known [102]. |
Akt/protein kinase B signaling inhibitor-2 (API-2) |
Unknown | Suppresses Akt kinase activity and activation | Does not affect upstream Akt activators [106]. |
Wortmannin | IC50 = 5 nM | Inhibits PI3-Kinase | Indirect effect on GSK-3β [97, 98]. |
LY294002 | IC50 = 1.4 μM | Inhibits PI3-Kinase | Likely affects ATP binding to kinase [98, 99]. |
Rapamycin | Unknown | Potentially inhibits S6K1 | mTOR pathway can also inhibit GSK3 [107, 108]. |
Differentiation-inducing factors (DIFs) |
Unknown | Enhances GSK-3β kinase activity and promotes nuclear localization | Reduces inhibitory phosphorylation and enhances activating phosphorylation [111, 112]. |
Retinoids | Unknown | Reduces inhibitory phosphorylation of GSK-3β | Promotes GSK-3β-dependent cyclin D1 degradation [80, 109]. |