GNF4877 is a highly potent inhibitor of DYRK1A and GSK3β, with IC50 values of 6 nM and 16 nM, respectively. This inhibition results in the prevention of nuclear factor of activated T-cells (NFATc) nuclear export and enhanced β-cell proliferation (with an EC50 of 0.66 μM for mouse β (R7T1) cells) [1].
体内研究
Elevated glucose levels and glucokinase activators (GKAs) enhance Ca2+ signaling in β-cells, leading to increased intracellular Ca2+ levels, which in turn activate calcineurin and facilitate the nuclear translocation of NFATc proteins. Remarkably, GNF4877 concentrations (0.1 μM, 0.3 μM), significantly lower than the EC50 for β-cell proliferation, induce proliferation in the presence of high glucose or pharmacological glucokinase activators. Additionally, augmenting intracellular Ca2+ levels with glibenclamide (a sulfonylurea receptor 1 inhibitor) or Bay K8644 (an L-type Ca2+ channel activator) exhibits additive effects with GNF4877 [1].
体外研究
Elevated glucose levels and glucokinase activators (GKAs) enhance Ca2+ signaling in β-cells, leading to increased intracellular Ca2+ levels, which in turn activate calcineurin and facilitate the nuclear translocation of NFATc proteins. Remarkably, GNF4877 concentrations (0.1 μM, 0.3 μM), significantly lower than the EC50 for β-cell proliferation, induce proliferation in the presence of high glucose or pharmacological glucokinase activators. Additionally, augmenting intracellular Ca2+ levels with glibenclamide (a sulfonylurea receptor 1 inhibitor) or Bay K8644 (an L-type Ca2+ channel activator) exhibits additive effects with GNF4877 [1].
搜索
