GNE-9605 is highly potent against LRRK2 in both biochemical (Ki = 2.0 nM) and cellular (IC50 = 19 nM) assays. In vitro human MDR1 permeability data, GNE-9605 exhibits excellent brain penetration in higher species.
In vivo
In vivo rat PK studies with GNE-9605 (1 mg/kg, p.o.) demonstrates a total plasma clearance of 26 mL/min/kg with excellent oral bioavailability (90%). In BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation, GNE-9605 (10 and 50 mg/kg, i.p.) inhibits in vivo LRRK2 Ser1292 autophosphorylation.
