GSK-2578215A is a potent and highly selective LRRK2 kinase inhibitor that possesses good blood-brain barrier (BBB) permeability with a high ratio of brain to plasma distribution in mice. GSK-2578215A was identified in a screen of GlaxoSmithKline’s KCS (a kinase-focused set of compounds for lead discovery) using a homogeneous time-resolved fluorescence (HTRF) assay that measured the inhibition of phosphorylation of the peptide substrate LRRKtide by baculoviral-derived recombinant 6His-Tev-LRRK2 (1326-2527). SAR and optimization of leads was performed using similar recombinant LRRK2 enzyme assays. GSK-2578215A exhibited biochemical IC50s of 10.9 and 8.9 nM against wild-type LRRK2 and LRRK2 [G2019S], respectively. The ability of GSK-2578215A to reduce phosphorylation levels of Ser910 and Ser935 in peripheral tissues on dosing to mice supports the notion that these phosphoepitopes can serve as markers of LRRK2 inhibitor activity in animal studies. Gene variants of the leucine-rich repeat kinase 2 (LRRK2) are associated with susceptibility to Parkinson's disease (PD). GSK-2578215A can be potentially used for the treatment of Parkinson's disease and other neurodegenerative diseases.