Description
GNF4877 is a highly potent and selective small molecule that promotes pancreatic β cell proliferation in rodent （EC50 ~0.66 µM）and human primary islets (EC50 ~0.54 µM), better than its analog GNF7156. It acts most likely as a result of combined inhibition of DYRK1A and GSK3B. GNF4877-treated human islets retain functionality in vitro and after transplantation into diabetic mice. Oral dosing of GNF4877 in diabetic mice induces β-cell proliferation, increases β-cell mass and insulin content, and improves glycaemic control. Biochemical, genetic and cell biology data point to Dyrk1a as the key molecular target. GNF4877 and its analog GNF7156 are the good chemical tools to support the feasibility of treating diabetes with an oral therapy to restore β-cell mass, and highlights a tractable pathway for future drug discovery efforts.
Product information
CAS Number: 2041073-22-5
Molecular Weight: 494.52
Formula: C25H27FN6O4
Chemical Name: (R)-1-(3-(3-amino-6-(2-fluoro-5-isopropoxyphenyl)pyrazine-2-carboxamido)pyridin-4-yl)piperidine-3-carboxylic acid
Smiles: CC(C)OC1=CC=C(F)C(=C1)C1=CN=C(N)C(=N1)C(=O)NC1=CN=CC=C1N1C[C@@H](CCC1)C(O)=O
InChiKey: UZIATSFXNVOVFE-OAHLLOKOSA-N
InChi: InChI=1S/C25H27FN6O4/c1-14(2)36-16-5-6-18(26)17(10-16)19-12-29-23(27)22(30-19)24(33)31-20-11-28-8-7-21(20)32-9-3-4-15(13-32)25(34)35/h5-8,10-12,14-15H,3-4,9,13H2,1-2H3,(H2,27,29)(H,31,33)(H,34,35)/t15-/m1/s1
Technical Data
Appearance: Solid Power.
Purity: ≥98% (or refer to the Certificate of Analysis)
Solubility: DMSO up to 100 mM
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.
Shelf Life: ≥12 months if stored properly.
Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.
Drug Formulation: To be determined.
HS Tariff Code: 382200
How to use
In Vitro:
GNF4877 was used at 2 µM concentration in beta cell proliferation assays.
In Vivo:
GNF4877 was orally dosed to mice at 50 mg/kg twice a day for 14 days.
References:
- Shen W, et al. Inhibition of DYRK1A and GSK3B induces human β-cell proliferation. (2015) Nat Commun. 6:8372.
Products are for research use only. Not for human use.
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