MLi-2 is a potent, highly selective, orally available, brain-penetrant inhibitor of LRRK2 with IC50 of 0.76 nM, pSer935 LRRK2 IC50 of 1.4 nM.
MLi-2 shows an IC50 of 3.4 nM in a radioligand competition binding assay, > 95-fold selectivity for over 300 kinases in addition to a diverse panel of receptors and ion channels.
MLi-2 signficantly reduces the ratio of phosphorylated Ser935 LRRK2 (pS935) to total LRRK2 in the mouse cortex in both single dose and 11-day in-diet studies.
MLi-2 significantly reduces pS935 in a dose dependent manner (1–100 mg/kg) 1 h post treatment in rats.
