2041073-22-5
2041073-22-5 structure
- Name: GNF-4877
- Chemical Name: GNF4877
- CAS Number: 2041073-22-5
- Molecular Formula: C25H27FN6O4
- Molecular Weight: 494.52
- Catalog: Signaling Pathways PI3K/Akt/mTOR GSK-3
- Create Date: 2019-12-08 17:09:19
- Modify Date: 2024-01-12 11:15:01
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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].
| Name | GNF4877 |
|---|---|
| Synonyms | GNF-4877 |
| Description | 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]. |
|---|---|
| Related Catalog | |
| Target |
GSK3β:16 nM (IC50) DYRK1A:6 nM (IC50) |
| In Vitro | 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: 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)[1] 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. |
| References |
| Molecular Formula | C25H27FN6O4 |
|---|---|
| Molecular Weight | 494.52 |
| Storage condition | -20°C |