– GNF2133 hydrochloride is a selective, effective, and orally active DYRK1A inhibitor, able to act on DYRK1A (IC50: 0.0062 μM) and GSK3β (IC50> 50 μM); GNF2133 hydrochloride showed good proliferative ability and efficacy in rat and human primary β cells. GNF2133 hydrochloride significantly improved glucose processing ability and increased insulin secretion. GNF2133 hydrochloride has the potential to study type 1 diabetes.