GNF4877

Research use only, not for human use.

GNF4877 is a potent DYRK1A and GSK3β inhibitor (IC50s: 6?nM and 16?nM).

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.

High glucose concentrations and glucokinase activators (GKAs) increase Ca2+ signalling in β-cells, and increase intracellular Ca2+ leads to activation of calcineurin and nuclear translocation of NFATc proteins. Indeed, 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. Finally, increasing intracellular Ca2+ with glibenclamide (a sulfonylurea receptor 1 inhibitor) or Bay K8644 (an L-type Ca2+ channel activator) show additive activity with GNF4877.

GNF4877 (50 mg/kg; oral gavage; twice a day; for 15 days; double transgenic RIP-DTA male mice) treatment induces β-cell proliferation, increases β-cell mass and insulin content, and improves glycaemic control. Animal Model:Double transgenic RIP-DTA male mice (Tg (Ins 2-rtTA) 2 Efr Tg (teto-DTA) 1 Gfi/J) with Doxycycline (28.8±2.4?g; 82±2 days) Dosage:50 mg/kg Administration:Oral gavage; twice a day; for 15 days Result:Induced β-cell proliferation, increased β-cell mass and insulin content, and improved glycaemic control.

——

Others

Other Targets

GSK3β|DYRK1A

——

——

2041073-22-5

494.52

C25H27FN6O4

>98% (HPLC)

DMSO:4.17 mg/mL (8.43 mM; Need ultrasonic and warming)

CC(C)OC1=CC(=C(C=C1)F)C2=CN=C(C(=N2)C(=O)NC3=C(C=CN=C3)N4CCC[C@H](C4)C(=O)O)N

——

(-20℃)

With Ice Pack

≥ 2 years