GNE-0877 significantly inhibits LRRK2 cellular activity with IC50 of 3 nM, and shows low turnover in human liver microsomes and hepatocytes. Besides, GNE-0877 is also a reversible CYP1A2 inhibitor with IC50 of 0.7 μM.
In vivo
In vivo, GNE-0877 shows good oral bioavailability and brain penetration. GNE-0877 inhibits in vivo LRRK2 Ser1292 autophosphorylation in BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation.
