GNF4877

GNF4877 is a small molecule inhibitor, a potent dual-specificity kinase inhibitor targeting DYRK1A (IC50=6 nM) and GSK3β (IC50=16 nM). This compound promotes β-cell proliferation by blocking NFATc nuclear export (EC50=0.66 μM for mouse R7T1 cells) and is primarily used for research on β-cell regeneration related to diabetes.

GSK-3β:16 nM, HT22 cells:16.3 μM, Pancreatic beta cell:0.54 μM (EC50), Pancreatic beta cell:0.19 mM (EC50), DYRK1 cellsA:6 nM

Methods: Mouse β-cells (such as R7T1 cells) were treated with low concentrations of GNF4877 (0.1, 0.3 μM) in combination with high glucose, glucokinase activators (GKAs), glibenclamide, or Bay K8644 to detect cell proliferation, Ca²⁺ signaling, and NFATc nuclear translocation.
Results: Low concentrations of GNF4877 promoted β-cell proliferation under high glucose or GKA stimulation; high glucose and GKAs enhanced Ca²⁺ signaling, activated calcineurin, and promoted NFATc nuclear translocation; glibenclamide or Bay K8644 increased intracellular Ca²⁺ and showed additive effects with GNF4877. [1]

Methods: A mouse β-cell model was used, and low concentrations of GNF4877 (0.1, 0.3 μM) combined with high glucose or glucokinase activators (GKAs) were applied to detect cell proliferation; the effects of high glucose and GKAs on Ca²⁺ signaling, calcineurin activation, and NFATc nuclear translocation were also evaluated; additionally, glibenclamide or Bay K8644 combined with GNF4877 were used to detect synergistic effects.
Results: Low concentrations of GNF4877 promoted β-cell proliferation under high glucose or GKA stimulation; high glucose and GKAs enhanced Ca²⁺ signaling, activated calcineurin, and promoted NFATc nuclear translocation; glibenclamide or Bay K8644 increased intracellular Ca²⁺ and showed additive effects with GNF4877. [1]

DMSO: 6.94 mg/mL (14.03 mM), Sonication is recommended.