GNF4877

SKU: orb1309621

Description

GNF4877 is a potent small molecule inhibitor of DYRK1A and GSK3β with IC50 values of 6 nM and 16 nM, respectively. It promotes β-cell proliferation by blocking NFATc nuclear export, making it a valuable research tool for studying diabetes and regenerative biology in both cellular and animal models.

Research Area

Cell Biology, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 2041073-22-5
• MW: 494.52
• Purity: 99.40%
• Formula: C₂₅H₂₇FN₆O₄
• SMILES: CC(C)Oc1ccc(F)c(c1)-c1cnc(N)c(n1)C(=O)Nc1cnccc1N1CCC[C@H](C1)C(O)=O
• Target: GSK-3,DYRK
• Solubility: DMSO:10 mg/mL (20.22 mM)

Bioactivity

• Target IC50:
  GSK-3β:16 nM|DYRK1 cellsA:6 nM|Pancreatic beta cell:0.19 mM (EC50)|Pancreatic beta cell:0.54 μM (EC50)|HT22 cells:16.3 μM
• In Vivo:
  In double transgenic RIP-DTA male mice, GNF4877 (50 mg/kg; oral gavage; twice a day; for 15 days) treatment induces β-cell proliferation, increases β-cell mass and insulin content, and improves glycaemic control.
• In Vitro:
  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. High glucose concentrations and glucokinase activators (GKAs) increase Ca2+ signaling in β-cells, and increase intracellular Ca2+ leads to activation of calcineurin and nuclear translocation of NFATc proteins. Finally, increasing intracellular Ca2+ with glibenclamide or Bay K8644 shows additive activity with GNF4877.

Storage & Handling

• Storage: keep away from moisture | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

DYRK, DYRK1A, Dual specificity tyrosine phosphorylation regulated kinase, Dual specificity tyrosine regulated kinase, GNF 4877, GNF4877, GNF-4877, Glycogen synthase kinase-3, Glycogen synthase kinase 3, GSK-3, GSK3, GSK3β, GSK-3β, Inhibitor, inhibit

Compound Identifiers

PubChem CID

139600315