tcsc3098 GNE0877

GNE0877 is a highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitor with an IC50 of 3 nM.

IC50 value: 3 nM [1]

Target: LRRK2

Invitrogen kinase-selectivity profiling(188 kinases) of aminopyrazole GNE0877 at 0.1 μM (145-fold overLRRK2 Ki) resulted in only four kinases showing greater than 50% inhibition (Aurora B = 51%, RSK2 = 52%, RSK4 = 62%, and RSK3 = 68%) and suggested that GNE0877 is a highly selective LRRK2 inhibitor. Furthermore, GNE0877 possessed a 212-fold biochemical-selectivity index over TTK (Ki= 150 nM), which was previously highlighted as an off-target kinase of concern because of the suggested role of TTK in the

maintenance of chromosomal stability. The in vivo rat clearance for inhibitor GNE0877 was within 2-fold of measured in vitro stability, and good oral bioavailability (88%) was achieved at 50 mg/kg following administration of a methylcellulose/tween (MCT) suspension.