GNF4877

SKU: orb1218505

Description

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.

Key Properties

• CAS Number: 2041073-22-5
• MW: 494.52
• Purity: >98% (HPLC)
• Formula: C₂₅H₂₇FN₆O₄
• SMILES: 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
• Target: GSK3β|DYRK1A
• Solubility: DMSO:4.17 mg/mL (8.43 mM; Need ultrasonic and warming)

Bioactivity

• 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. 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.
• 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

GSK3β|DYRK1A