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DYRK1-IN-1 is a highly selective and ligand-efficient DYRK1A inhibitor. DYRK1-IN-1 inhibits DYRK1A phosphorylation activity with an IC 50 value of 220 nM. DYRK1-IN-1 exhibits good permeability and cellular activity without P-glycoprotein liability that can be used for the research of central nervous system penetrant DYRK1A chemical probe [1].