| Bioactivity | GNF4877 is a potent DYRK1A and GSK3β inhibitor with IC50s of 6 nM and 16 nM, respectively, which leads to blockade of nuclear factor of activated T-cells (NFATc) nuclear export and increased β-cell proliferation (EC50 of 0.66 μM for mouse β (R7T1) cells)[1]. | ||||||||||||
| Invitro | 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[1]. | ||||||||||||
| In Vivo | 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[1]. Animal Model: | ||||||||||||
| Name | GNF4877 | ||||||||||||
| CAS | 2041073-22-5 | ||||||||||||
| Formula | C25H27FN6O4 | ||||||||||||
| Molar Mass | 494.52 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Shen W, et al. Inhibition of DYRK1A and GSK3β induces human β-cell proliferation. Nat Commun. 2015 Oct 26;6:8372. |
GNF4877
CAS: 2041073-22-5 F: C25H27FN6O4 W: 494.52
GNF4877 is a potent DYRK1A and GSK3β inhibitor with IC50s of 6 nM and 16 nM, respectively, which leads to blockade of
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