| Identification | Back Directory | [Name]
GNF4877 | [CAS]
2041073-22-5 | [Synonyms]
GNF4877
CID 139600315
CID 139600315(GNF-4877)
3-Piperidinecarboxylic acid, 1-[3-[[[3-amino-6-[2-fluoro-5-(1-methylethoxy)phenyl]-2-pyrazinyl]carbonyl]amino]-4-pyridinyl]-, (3R)- | [Molecular Formula]
C25H27FN6O4 | [MDL Number]
MFCD32263043 | [MOL File]
2041073-22-5.mol | [Molecular Weight]
494.52 |
| Chemical Properties | Back Directory | [Boiling point ]
669.7±55.0 °C(Predicted) | [density ]
1.367±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: 4.17 mg/mL (8.43 mM and warming) | [form ]
Solid | [pka]
2.82±0.70(Predicted) | [color ]
Light yellow to yellow | [InChIKey]
UZIATSFXNVOVFE-OAHLLOKOSA-N | [SMILES]
N1(C2C=CN=CC=2NC(C2=NC(C3=CC(OC(C)C)=CC=C3F)=CN=C2N)=O)CCC[C@@H](C(O)=O)C1 |
| Hazard Information | Back Directory | [Uses]
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]. | [Biological Activity]
GNF4877 is a potent inhibitor of DYRK1A and GSK3β with IC50 values of 6 nM and 16 nM, respectively, resulting in blocked NFATc nuclear export and increased β-cell proliferation (EC50 for mouse β (R7T1) cells 0.66 μM). | [in vitro]
High glucose concentrations and glucokinase activators (GKAs) increase Ca 2+ signalling in β-cells, and increase intracellular Ca 2+ leads to activation of calcineurin and nuclear translocation of NFATc proteins. Indeed, concentrations of GNF4877 ((0.1 μM, 0.3 μM) well below the EC 50 for β-cell proliferation are able to induce proliferation in the presence of high glucose or pharmacological activators of glucokinase. Finally, increasing intracellular Ca 2+ with glibenclamide (a sulfonylurea receptor 1 inhibitor) or Bay K8644 (an L-type Ca 2+ sup> channel activator) show additive activity with GNF4877. | [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. | | [target]
| GSK3β 16 nM (IC 50 ) | DYRK1A 6 nM (IC 50 ) | | [IC 50]
GSK3β: 16 nM (IC50); DYRK1A: 6 nM (IC50) | [References]
[1] Shen W, et al. Inhibition of DYRK1A and GSK3β induces human β-cell proliferation. Nat Commun. 2015 Oct 26;6:8372. DOI:10.1038/ncomms9372 |
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| Company Name: |
DC Chemicals Gold
|
| Tel: |
021-58447131 13564518121 |
| Website: |
www.chemicalbook.com/showsupplierproductslist927327/0_en.htm |
| Company Name: |
cjbscvictory
|
| Tel: |
13348960310 |
| Website: |
https://www.weikeqi-biotech.com/ |
|