GNE-9065 is an orally bioavailable and potent inhibitor of leucine-rich repeat kinase 2 (LRRK2; IC50 = 18.7 nM). It is selective for LRRK2 over 178 kinases, inhibiting only TAK1-TAB1 >50% at a concentration of 0.1 μM. GNE-9065 (10 and 50 mg/kg) inhibits LRRK2 Ser1292 autophosphorylation in BAC transgenic mice expressing human LRRK2 protein with the G2019S mutation found in families with autosomal Parkinson’s disease.
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