FX2149 improved the brain penetration and inhibition of LRRK2 GTP binding and kinase activities.

<p>FX2149 (10 mg/kg) and 68 (10 and 20 mg/kg) were injected intraperitoneally into G2019S-LRRK2 BAC transgenic mice at 6–12 weeks of age for 1 hour. There were 6 mice in each experimental group. The brain homogenates were used to detect LRRK2 GTP-binding and kinase activities. A and B, LRRK2 GTP-binding assays. C and D, LRRK2 phosphorylation assays using anti-phospho-LRRK2 antibodies. E and F, FX2149 reduced G2019S-LRRK2-induced 4E-BP phosphorylation determined by anti-phospho-4E-BP western blot analysis. Ntg: non-transgenic mouse. *<i>p</i> < 0.05 by ANOVA compared with G2019S-LRRK2 transgenic mice treated with vehicle.