Discovery of potent small molecule inhibitors of DYRK1A
by structure-based virtual screening and bioassay

In this study, six novel dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) inhibitors
with IC50 values ranging from 1.51 to 88.13 lM were successfully identified through virtual screening
and in vitro plus cell based bioassay. Compound 5 with IC50 value of 1.51 lM is the most potent hit
against DYRK1A in vitro, while compound 3 exhibited the most potent activity in cultured cells. The inhibition
mechanism was explored by molecular docking approach. This study may provide a start point for
further mechanism based study as well as discovery of drug candidate against Down syndrome (DS).