DYRK1-IN-1 is a highly selective and ligand-efficient DYRK1A inhibitor that inhibits DYRK1A phosphorylation activity with an IC50 value of 220 nM. It exhibits good permeability and cellular activity without P-glycoprotein liability, making it suitable for research on central nervous system penetrant DYRK1A chemical probes [1].

DYRK1-IN-1 is a potent inhibitor of DYRK1A phosphorylation, achieving inhibition with an IC 50 value of 220 nM and demonstrating an ability to inhibit tau phosphorylation at an IC 50 of 0.59 μM. This compound exhibits good permeability and cellular activity, devoid of P-glycoprotein liability. It also possesses excellent physicochemical characteristics, including high enzymatic potency, favorable aqueous solubility, outstanding kinome selectivity, and robust on-target in vitro inhibition efficacy. In HEK293 cells, DYRK1-IN-1 shows satisfactory cellular activity with an IC 50 of 434 nM, in comparison to an enzymatic IC 50 of 75 nM.

DYRK1-IN-1 (1 mg/kg; i.v.) exhibits high clearance in Sprague Dawley rats during pharmacokinetic analysis.