GNF2133 is a potent, selective and orally active DYRK1A inhibitor with IC 50 s of 0.0062, >50 µM for DYRK1A and GSK3β, respectively. GNF2133 shows good proliferation potency and efficacy on rat and human primary β-cell. GNF2133 significantly improves glucose disposal capacity and increases insulin secretion. GNF2133 has the potential for the research of type 1 diabetes In Vivo GNF2133 (30 mg/kg; p.o.) shows good oral absorption with oral bioavailability of 22.3% . GNF2133 (30 mg/kg; p.o.; once a day for 5 days) shows the ability to proliferate β-cells in vivo . GNF2133 (3, 10, 30 mg/kg) significantly improves glucose disposal capacity and increased insulin secretion in RIP-DTA mice . Pharmacokinetic Parameters of GNF2133 in CD-1 mice . plasma (iv) plasma (po) pancreas (po) CL (mL/min/kg) 23.5 / / V ss (L/kg) 11 / / AUC (h·nM) 3268 10974 144420 C max (nM) 1977 1675 13319 t max Form:Solid IC50& Target:DYRK1A 0.0062 μM (IC 50 ) GSK3β >50 μM (IC 50 )