Putative therapeutic agents for the learning and memory deficits of people with Down syndrome

A novel series of DYRK1A inhibitors were identified by combination of in silico screening, in vitro assay, and cell-based screenings. Mental retardation is the most common and debilitating condition for individuals with Down syndrome (DS). The hyper-activation of DYRK1A by overexpression causes significant learning and memory deficits in DS-model mice. Thus far, no mechanism-based drug has been developed to address this. After a combination of in silico and in vitro screenings, two DYRK1A inhibitors were isolated that are active in a cell-based assay. Further optimization could lead to a novel drug discovery that could address DS learning and memory deficits.