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Biological Activity:

GNF7156 is a highly potent and selective small molecule that promotes pancreatic β cell proliferation in rodent （EC50 ~2.2 μM）and human primary islets (EC50 ~0.76 μM). It acts most likely as a result of combined inhibition of DYRK1A and GSK3B. GNF7156-treated human islets retain functionality in vitro and after transplantation into diabetic mice. Oral dosing of GNF7156 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. GNF7156 is a good chemical tool 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.

How to Use:

In vitro: GNF7156 was used at 6.7 μM concentration in beta cell proliferation assays.
In vivo: GNF7156 was orally dosed to mice at 50 mg/kg twice a day for 14 days.

Reference:

• 1. Shen W, et al. Inhibition of DYRK1A and GSK3B induces human β-cell proliferation. (2015) Nat Commun. 6:8372.?