ZJCK-6-46 (32) is a potential orally active DYRK1A inhibitor (IC50= 0.68 nM) with favorable CNC permeability. It downregulates tau phosphorylation and improves cognitive impairments by significantly reducing the expression of phosphorylated tau proteins and neuronal loss.

DYRK3:17.48 nM, CLK4:1.80 nM, DYRK1A:0.68 nM, CLK1:1.68 nM, DYRK4:401.3 nM, DYRK1B:1.02 nM, DYRK2:14.18 nM, CLK3:38.91 nM

ZJCK-6-46(32,20-30 mg/kg,口服,OA(Okadaic acid)诱导的(MOD)小鼠)在OA诱导的小鼠中显著降低了CA1区和DG区p-Tau thr212的表达水平.