GNF4877 是一种 DYRK1A (IC50:6 nM) 和 GSK3β (IC50:16 nM) 抑制剂。 它导致激活 T 细胞核因子核输出的阻断和 β 细胞增殖细胞增加。

GNF4877 is a potent DYRK1A and GSK3β inhibitor (IC50s: 6 nM and 16 nM). It leads to blockade of nuclear factor of activated T-cells (NFATc) nuclear export and increased β-cell proliferation cells.

Concentrations of GNF4877 (0.1?μM, 0.3?μM) well below the EC50 for β-cell proliferation are able to induce proliferation in the presence of high glucose or pharmacological activators of glucokinase. High glucose concentrations and glucokinase activators (GKAs) increase Ca2+ signaling in β-cells, and increase intracellular Ca2+ leads to activation of calcineurin and nuclear translocation of NFATc proteins.?Finally, increasing intracellular Ca2+ with glibenclamide or Bay K8644 shows additive activity with GNF4877.

In double transgenic RIP-DTA male mice, GNF4877 (50 mg/kg; oral gavage; twice a day; for 15 days) treatment induces β-cell proliferation, increases β-cell mass and insulin content, and improves glycaemic control.

2041073-22-5

C25H27FN6O4

494.52

DMSO:4.17 mg/mL (8.43 mM),Need ultrasonic and warming
Powder: -20°C for 3 years
In solvent: -80°C for 2 years